Sex steroids were found to affect both murine and avian immune systems. Female and male (NZB X NZW)F1 mice were castrated at 2 weeks of age and given Silastic implants containing either dihydrotestosterone or estradiol. Four weeks following treatment, the thymuses were studied for cell cycle kinetics and for the presence of various cell surface antigens using fluorescein-conjugated antisera and flow cytometric techniques. Estradiol therapy resulted in an increase in mature thymocytes, that is, thymocytes that had decreased peanut agglutinin receptors and decreased Thy 1 antigens on their surfaces. Additional studies with anti-Lyt 1 and 2 indicated that these mature thymocytes were of the "helper" rather than the "suppressor" phenotype. Estradiol therapy resulted in an increase in the percentages of proliferating cells in the spleen and a decrease in the percentages of proliferating cells in the thymus. In contrast, in the avian system, estradiol had little effect on proliferation in immunological organs. Dihydrotestosterone was a potent inhibitor of proliferation in the avian bursa. These results indicate that sex hormones have specific effects on different immune cell subpopulations. In the murine system the male is the heterogametic sex but in the avian system the female is the heterogametic sex. Based upon the present and previous studies, we suggest that the primary modulating hormone for immunological sex effects in the mammal is estrogen, whereas in the bird it is androgen.