5-fluorouracil and actinomycin D were given, single and combined, to rats. The nucleolar ultrastructure was examined in liver, pancreas, spleen, kidney cortex, adrenal cortex, in epithelial and smooth muscle cells of the small intestine and in the Purkinje cells of the cerebellum. 5-fluorouracil, given alone, provoked changes in all tissues examined. Actinomycin D, given alone, gave changes in all tissues examined, except the cerebellum. Treatment with fluorouracil prior to actinomycin delayed and modified the effect of the latter drug in all tissues examined.