The functional significance of androgen receptors in thymocytes is unknown. To investigate whether such receptors might mediate androgen-induced effects on thymocyte proliferation or differentiation we examined mice bearing a known defect in the gene coding for the androgen receptor. This mutation, termed testicular feminization (Tfm/Y), renders these mice resistant to the action of androgenic hormones. Testicular feminization mice were found to have large thymuses that were an average of 2.8 times as heavy as those of their unaffected male litter mates, and contained up to 36 times as many thymocytes. Similar findings were observed when Tfm mice were compared with C57Bl/6 control mice. Thymocytes from androgen-resistant mice produced several times more interleukin 2 in culture than did thymocytes from control mice. A small but significant reduction in the population of cells bearing neither CD4 nor CD8 surface markers ('double negatives') was observed in the androgen-resistant mice. These data indicate that androgen resistance is associated in the Tfm/Y mouse with alterations in thymocyte number, phenotype, and function that may be attributable to lack of androgen action during thymic development.