LeuM5 antigen (CD11c, p150.95) expression, widely used as an immunodiagnostic marker for B-cell hairy cell leukemia, was examined on benign, normal peripheral blood T cells before and after stimulation in vitro with phytohemagglutinin and on a large, diverse panel of 73 T-cell neoplasms. Resting T cells lacked LeuM5. Intracytoplasmic LeuM5 was detectable at 3 to 4 days and surface membrane LeuM5 was detectable continuously between 5 and 17 days on greater than or equal to 20% CD3 cells (maximum, 42% CD3 cells at 10 days) after activation. Two-color flow cytometric analysis of the activated T cells demonstrated that a maximum of 60% CD8 but only 25% CD4 cells expressed LeuM5; the mean percentage of LeuM5+ CD8 cells was 44% compared with 12% LeuM5+ CD4 cells. A variable proportion of the neoplastic T cells in 19 of 73 (26%) T-cell neoplasms were LeuM5+. Twelve of 18 CD4-CD8+ (67%) but only 5 of 40 CD4+ CD8- T-cell neoplasms expressed LeuM5. These studies demonstrate that the LeuM5 antigen is 1) expressed in association with T-cell activation, 2) preferentially expressed by activated CD8 cells, and 3) variably expressed by neoplastic T cells, but particularly by those exhibiting the CD4- CD8+ phenotype.