Circulating T-lymphocyte subpopulations were enumerated in 65 patients with histoplasmosis and correlated with the different clinical manifestations of the disease. Acute pulmonary histoplasmosis, rheumatologic, disseminated, and chronic inflammatory manifestations of histoplasmosis were all associated with a significant elevation above normal of OKT8+ (suppressor-cytotoxic) lymphocytes and a significantly lower than normal OKT4+ (helper-inducer)-lymphocyte to OKT8+-lymphocyte ratio. In contrast, cavitary disease was associated with an increase in OKT4+ lymphocytes, a decrease in OKT8+ lymphocytes, and a higher than normal OKT4/OKT8 ratio. Clinical recovery was associated with normalization of these values. Functional activity determined by coculture techniques correlated closely with T-lymphocyte subset measurements. These distinct subset abnormalities may help monitor immunological aspects of disease activity.