Peripheral blood T lymphocyte subsets were measured by flow cytometry in 122 patients with leprosy, in 23 normal controls, and in 27 patients with systemic lupus erythematosus (SLE). Active lepromatous patients not in reaction showed a significant lymphopenia and a significant proportionate reduction in the number of OKT3-positive (pan T), OKT4-positive (helper/inducer), and OKT8-positive (suppressor/cytotoxic) cells, but no alteration in distribution as judged by percentage and no abnormality in the helper: suppressor ratio. Borderline lepromatous subjects not in reaction had a significant selective deficiency in the number of cells of the OKT4-positive subset, with a significant but secondary lymphopenia and OKT3-positive cytopenia, a pattern similar to that found in SLE patients. Patients undergoing reversal reactions had a selective deficiency in the OKT4-positive subset in both absolute numbers and as a percentage of total lymphocytes, and a secondary deficiency in the percentage of OKT3-positive cells. No abnormalities were demonstrated in patients with active erythema nodosum leprosum, lepromatous patients with long-term treatment, and untreated or treated borderline tuberculoid patients.