The lymphocyte subpopulations in the peripheral blood of 37 patients with retinitis pigmentosa (RP) and 24 controls were analyzed with the Leu series of monoclonal antibodies in conjunction with fluorescence-activated cell-sorter analysis. The peripheral blood lymphocytes (PBLs) from all RP genetic types had a significantly reduced frequency of Leu-4-positive T lymphocytes than controls, and a small but significant reduction in the frequency of Leu-3a-positive T lymphocytes was seen in patients with RP with the dominant trait. The reduced T-cell population seemed to be associated with an increased frequency of Leu-11a-positive cells. The PBLs from patients with RP did not react to retinal S-antigen, as assessed by the lymphocyte transformation or interleukin-2 assays. We conclude that patients with RP, although not clinically immunologically compromised, have a significantly reduced frequency of T lymphocytes in their PBLs. Furthermore, our study did not demonstrate reactivity to retinal tissue in PBLs from patients with RP.