Progesterone, estradiol, testosterone, cortisol, and 11-desoxycortisol (compound S) were added to cultures of human lymphocytes stimulated with phytohaemagglutinin (PHA) and purified protein derivative (PPD). The immunosuppressive effect of cortisol was verified and the three sex-steroid hormones also were found to inhibit lymphocyte transformation although at concentrations higher than for cortisol. Compound S, a steroid of low biological potency, also had immunosuppressive activity. At concentrations (0-01-1-0 microng/ml), progesterone, oestrogen, testosterone, and Compound S augmented the transformation response to PPD but not to PHA. Marked variation from individual to individual in the suppressive effects of all the steroids were noted. The clinical implications of immunosuppression by the sex steroid hormones are discussed.