The effects of substantia nigra lesions on the volume densities of islet cells and on the content of insulin and glucagon in the pancreas were examined using five groups of age-matched, Sprague-Dawley rats. Two groups received bilateral substantia nigra lesions using intrathecal injections of either a low (6 micrograms/hemisphere) or a high (12 micrograms/hemisphere) dose of 6-hydroxydopamine. Rats given sham lesions served as controls for the effects of the neurotoxic drug. These three groups, plus a fourth consisting of unoperated controls, were provided with a high-fat diet to minimize lesion-induced alterations of food intake and body weight. Eleven weeks after lesion placement, tissue was collected from all animals for the assessment of islet cell volume densities and the pancreatic content of insulin and glucagon. Plasma samples also were obtained to determine the levels of glucose, insulin, and glucagon. Data from those animals were compared with that obtained from a fifth group, termed "pre-lesion controls", sacrificed at the beginning of the experiment. Linear-scan morphometry documented an increase of B-cell volume density in the pancreas of non-lesioned rats over the 11-week period (p less than 0.05). However, the volume density of B cells in the pancreas of lesioned animals did not increase compared with that of pre-lesion controls. In terms of A or D cells, no significant differences of volume density were found between the five groups. Compared with that of the pre-lesion controls, pancreatic insulin and glucagon content increased in the lesioned and neurally-intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)