MRL/lpr and NZB X NZW F1 mice were neonatally thymectomized or treated with androgens from 2 weeks of age, and their natural histories were studied. Neonatal thymectomy of MRL/lpr mice led to marked reduction in the usual massive lymphadenopathy as well as significant reduction in antibodies to native DNA and prolonged survival. In contrast, neonatal thymectomy of NZB X NZW F1 mice led to accelerated disease. Androgen therapy of both mice led to reduced anti-DNA and prolonged survival. This occurred in the MRL/lpr mice without significant reduction in lymphadenopathy. Taken together, these studies suggest that different T cell abnormalities may underlie the development of autoimmunity in MRL/lpr and NZB X NZW F1 mice, but that disease may be expressed through a common androgen-sensitive pathway.