We investigated effects of sex steroids and analogs (estradiol, DES, norgestrel, progesterone, medroxyprogesterone, and testosterone) on the proliferation and survival of 10 human leukemia/lymphoma cell lines (HL-60, K562, U937, CEM, KG-1, Jurkat, U266, H929, PA and SUNHL). Micromolar concentrations of sex steroids exerted cytostatic and cytotoxic effects on all cell lines tested, irrespective of their sensitivity to glucocorticoids. The order of potency of sex hormones was: DES > progesterone > or = medroxyprogesterone > testosterone > estradiol >> norgestrel. For progesterone and estradiol, cytostatic effects can be achieved at lower concentrations than cytotoxic effects. The most potent agent, DES, exerted half maximal cytotoxic activity at a median concentration of 4 microM (for 10 leukemia cell lines). Our results provide a basis for the potential therapeutic use of estrogens and progestins in glucocorticoid-resistant leukemias and lymphomas.