Cell-mediated immunity to retinal antigens as determined by in vitro assays has been detected in a variety of retinal degenerative and retinal destructive conditions. The authors studied the in vitro reactivity to the soluble retinal S antigen of peripheral blood mononuclear cells from patients with simplex and multiplex retinitis pigmentosa (RP) and Usher's syndrome along with normal controls. The cellular stimulation index (SI) was calculated by comparing 3H-thymidine incorporation in cells exposed to either purified S antigen, crude whole human retinal antigen, or human choroidal antigen with that in unstimulated control cultures. Eight of 15 patients with RP and 5 of 6 with Usher's had a SI greater than the tolerance limits of normal values. These results indicate that the immune system may be involved either primarily or secondarily in RP.