Interleukin-1β (IL-1β), which modulates cell proliferation and differentiation in a number of cell types, is present in human endometrial stromal cells. However, both the function of IL-1β in endometrium and the factors that modulate its expression in endometrial stromal cells are unknown. To examine the effects of IL-1β on decidualization, human proliferative endometrial stromal cells were cultured for 12 days in medium (Dulbecco's Modified Eagle's medium with 2% fetal bovine serum) containing 1 μM medroxyprogesterone acetate, 10 nM estradiol, and 1 μM prostaglandin E2 (PGE2) with and without IL-1β (17 pg/ml). Morphologic changes as well as release of prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) were used as markers of decidualization. Morphologic analysis of cells exposed to IL-1β revealed incomplete decidualization. In addition, cells exposed to IL-1β released 40% less PRL and 85% less IGFBP-1 than cells cultured in the absence of IL-1β, and the PRL mRNA content of the IL-1β- exposed cells was decreased by 68%. A possible role for ovarian steroids in the modulation of IL-1β expression in the endometrium is suggested by the increase in IL-1β mRNA that occurs in late secretory endometrium and by the induction of IL-1 by estrogen and progesterone in the mouse uterus. To examine whether or not IL-1β mRNA expression is increased in cells of human endometrial stroma during decidualization, an enriched fraction of proliferative endometrial stromal cells was cultured for 18 days in control medium (no steroids or PGE2) or medium containing 1 μM medroxyprogesterone acetate, 10 nM estradiol, and 1 μM PGE2. At Day 18, the IL-1β mRNA content of the cells of the decidualized endometrial stroma, detected by semiquantitative reverse-transcriptase polymerase chain reaction, was 4.6- fold greater than that of control cells. These results suggest that endometrial stromal IL-1β, which is increased with decidualization, may act in an autocrine/paracrine manner to modulate the degree of decidualization.