Immunohistochemical techniques using monoclonal antibodies to T lymphocyte subsets were used to characterize granulomas caused by Paracoccidioides brasiliensis. Punch biopsies of skin or mucosa from eight patients and of lymph nodes from two patients with disseminated paracoccidioidomycosis were studied. The T lymphocytes were distributed either in a localized pattern related to epithelioid granulomas or in a diffuse arrangement, predominantly around the vessels. In the granulomas, T cells formed a peripheral mantle surrounding central aggregates of macrophages. The majority of lymphocytes were T-helper cells with few suppressor cells. In contrast, patients presented with a decreased number of peripheral T-helper lymphocytes and a corresponding decrease in helper-suppressor cell ratios. There was no clear-cut relationship between tissue helper-suppressor cell ratios and the level of cellular immunodepression of the patients. The lowest P. brasiliensis antibody titers were detected in patients with the highest tissue helper-suppressor cell ratios. The distribution pattern of T lymphocytes in P. brasiliensis granulomas, with a predominance of helper phenotype, suggests that these cells are actively involved in the disease process.