The effect of RU 486 [17β-hydroxy-11β-(4-dimethylamino-phenol)17α-(prop-l-ynyl)estra-4,9diene-3-one]on [³H]thymidine incorporation into Concanavalin-A-stimulated human peripheral blood mononuclear cells and its influence on the suppressive effects of cortisol and progesterone were investigated. Cortisol suppressed lymphocyte thymidine incorporation at 10⁻⁵, 10⁻⁶, and 10⁻⁷ M (17.6%, 20%, and 38% of control, respectively; P < 0.01). Cortisol-induced suppression was reversed when low concentrations of RU 486 (10⁻⁷ and 10⁻⁶ M) were added. RU 486 at 10⁻⁵ M further suppressed lymphocyte thymidine incorporation when added to cultures with cortisol. Progesterone significantly inhibited lymphocyte thymidine incorporation at 10⁻⁵ M (8.2% of control; P < 0.01). No reversal of progesterone-induced suppression of thymidine incorporation was seen when RU 486 was added to cultures; rather, further suppression of thymidine incorporation was seen. RU 486 alone in culture at concentrations achieved therapeutically (10⁻⁵ M) significantly inhibited thymidine incorporation (7.2% of control; P < 0.01). These findings suggest that RU 486 may have dosedependent mixed agonist/antagonist effects on cortisol-induced immunosuppression. The lack of an antagonist effect of RU 486 on progesterone suggests that progesterone’s immunosuppressive effects may not be receptor mediated. Finally, our findings would suggest that some immunosuppression may be seen at currently used doses of RU 486. (J Clin Endocrinol Metab69: 1195, 1989)