Injections of the retrograde tracer, wheat germ agglutinated-horseradish peroxidase were placed in the substantia nigra, in adjoining dopamine-containing cell groups A8 and A10, and in the internal and external parts of the pallidal complex of 20 cats in order to identify the compartmental origins of striatal efferent projections to the pallidum and midbrain. Patterns of retrograde cell-labeling in the caudate nucleus were analysed with respect to its striosomal architecture as detected in sections stained for acetylcholinesterase. Where possible, a similar compartmental analysis of cell-labeling in the putamen was also carried out. In 15 cats anterograde labeling in the striatum was studied in the sections stained with wheat germ agglutinated-horseradish peroxidase or in autoradiographically treated sections from cases in which [ 35S]methionine was mixed with the wheat germ agglutinated-horseradish peroxidase in the injection solution. Predominant labeling of projection neurons lying in striosomes (usually with some labeling of dorso-medial matrix neurons) occurred in a subset of the cases of nigral injection, including all cases ( n = 9) in which the injection sites were centered in the densocellular zone of the substantia nigra pars compacta [Jiménez-Castellanos J. and Graybiel A.M. (1987) Neuroscience 23, 223–242.] Dense labeling of neurons in the extrastriosomal matrix, with at most sparse labeling of striosomal neurons, occurred in all cases of pallidal injection ( n = 8) and in two cases of nigral injection in which the injection sites were lateral and anterior to the densocellular zone. Mixed labeling of striosomal and matrical neurons occurred in a third group of cases in which the injection sites were lateral to the densocellular zone but close to it. In a single case with an injection site situated in the pars lateralis of the substantia nigra, there was preferential labeling of striosomal neurons in the caudal caudate nucleus but widespread labeling of neurons in both striosomes and matrix in the putamen. A second type of compartmental ordering of projection neurons was found in the extrastriosomal matrix of the striatum. In cases of pallidal and nigral injection, there were gaps in cell labeling that did not match striosomes precisely, and often clusters of labeled cells appeared that did not correspond to acetylcholin-esterase-poor striosomes but, instead, to patches of matrix. Especially prominent were clusters beside striosomes. There was a topographic ordering of striatal projection neurons both in the striosomes and in the extrastriosomal matrix according to their dorsoventral and latitudinal positions. Intranigral injections of [ 35S]methionine mixed with wheat germ agglutinated-horseradish peroxidase, and nigral cases in which anterograde and retrograde labeling with wheat germ agglutinated-horseradish peroxidase were differentiable, demonstrated patterns of conjoint anterograde and retrograde labeling of corresponding striosomes or of corresponding extrastriosomal matrix. These findings suggest the presence of reciprocal links between the striatum and the substantia nigra pars compacta, or at least links between the striatum and parts of the pars compacta and pars reticulata lying very close to one another. By contrast, injections centered in cell group A8 elicited very little retrograde labeling in either the dorsal or the ventral striatum, and although injections placed in the ventral tegmental area led to extensive retrograde labeling of parts of the ventral striatum, there was little retrograde labeling of the dorsal striatum. Thus the projections from cell groups A8 and A10 to the dorsal striatum may only be weakly reciprocated, if at all. We conclude the following: (1) Striosomal ordering is followed by each major category of striatal efferent connection, but non-striosornal ordering of striatal projection neurons also occurs. (2) The extrastriosomal matrix of the striatum is specialized for conveying information to the two segments of the globus pallidus and the lateral (probably reticular) part of the substantia nigra. (3) Within the matrix, neurons projecting to the pallidum and to the substantia nigra are subject to a form of non-striosomal but striosome-like compartmentalization. (4) The striosomal system of the striatum is specialized for transmitting information from the striatum to the substantia nigra, though a small striosomal output to the pallidum is not excluded by these findings. (5) Cell group A9 may participate in reciprocating striatonigral-nigrostriatal loops, but the projections from cell groups A8 and A10 to the dorsal striatum may lack strong direct return connections.