Enteric infections are common in homosexual men. We have characterized the phenotypic distribution of small intestinal mononuclear cells among healthy homosexual men, homosexual men with lymphadenopathy syndrome, homosexual men with acquired immunodeficiency syndrome (AIDS), and a group of healthy heterosexual men. Total numbers of T lymphocytes in the small intestinal mucosa were significantly decreased in homosexual men with lymphadenopathy syndrome and AIDS. This decrease was most striking among the Leu-3a T-cell subset usually associated with helper/inducer function. The proportion of mucosal T cells reacting with Leu-2a (cytotoxic/suppressor phenotype) and lymphoid cells having the T305 antigen was significantly increased only in AIDS subjects. Both lymphadenopathy syndrome and AIDS subjects had a significant reversal of the normal mucosal helper/suppressor T-cell ratio. Mucosal helper/suppressor T-cell ratios and the distribution of mucosal mononuclear cells were normal in healthy homosexual men, although the same individuals had reversed helper/suppressor ratios among circulating T cells. Enteric infections in healthy homosexual men likely reflect sexual practices, and not a primary abnormality in intestinal mucosal immunity. In contrast, specific abnormalities in intestinal mucosal immunity may contribute to the persistent and opportunistic enteric infections that occur in AIDS.