Autoimmune oophoritis that develops in A/J mice after neonatally thymectomy (NTx) was prevented by a single intraperitoneal injection of spleen cells or thymocytes from normal adult female mice. Prevention of oophoritis was achieved when spleen cells were given within 2 wk after Tx. When spleen cells were obtained from neonatally oophorectomized mice, four times more cells were required for the prevention of oophoritis, but those from the mice oophorectomized on day 7 after birth had equivalent capacity to prevent oophoritis to those from normal female mice. The spleen cells from normal A/J mice that prevented the development of oophoritis in NTx A/J mice were Thy-1+, Lyt-1+,23-, Ia-, Qa-1-, sensitive to in vitro irradiation with 400 rad, resistant to administration of cyclophosphamide or anti-thymocyte serum, and were not eliminated by adult thymectomy. Thymocytes with oophoritis-preventing capacity were also found to be Lyt-1+,23- and TL- 1,2,3-. These results seem to correlate well with the finding that the Lyt-1 subpopulation is substantially decreased in NTx mice. The results suggest that, in this post-thymectomy autoimmune oophoritis, NTx abrogates the Lyt-1 T cell subpopulation that serves as suppressive or regulatory cells over developing self-reactive cells directed toward ovarian antigens, and eventually may cause autoimmune oophoritis.