Sexual dimorphism is a routinely encountered but previously unreported feature of the normal rat mammary gland. Forty male and 40 female F344 rats, 19 weeks of age, were examined retrospectively to document histologic differences that are very apparent when mammary glands of males and females of the same age are compared. Development of the mammary gland starts in utero, and there is reported to be little morphologic difference between males and females at birth. By 19 weeks of age, however, the differences are very noticeable. The mammary glands of females, comprised of scattered tubular ducts and alveolar structures that have distinct lumina lined, usually, by a single layer of cuboidal epithelium, are characterized as tubuloalveolar. In young males, mammary tissue is generally more florid than in females of the same age. There are, scattered within the hypodermis, larger, more contiguous, lobular groups of cells that are distinct for their lack of obvious tubular or ductal orientation. The cells, arranged into alveoli, are generally characterized by abundant, foamy, eosinophilic cytoplasm containing distinct, variably-sized vacuoles. Alveolar lumina are mostly indistinct but may contain evidence of secretory activity. To emphasize the importance of this difference, selected results of a routine toxicity study are discussed in which the mammary glands of male rats, exposed for 52 weeks to cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methyl-aminobenzamide, a reported dopamine antagonist, underwent distinctive histomorphologic changes. As a result of exposure to this compound, the lobuloalveolar structure described as normal for male rats assumed characteristics of a tubuloalveolar morphology indistinguishable from that seen in the unexposed females.(ABSTRACT TRUNCATED AT 250 WORDS)