It has been hypothesized that the activated peritoneal macrophages of endometriosis, rather than being a response to ectopic endometrium, may contribute to its pathogenesis. This study attempts to define the effect of macrophage-derived growth factors on endometrial stromal cell growth in vitro, as well as the interaction between estrogen and these growth factors. Mouse endometrial stromal cells were prepared and cultured in either a serum-containing, insulin-free medium or a serum-free, insulin-containing medium, and the effects of adding 10% macrophage-conditioned medium on [3H]thymidine incorporation were assessed. Results indicate that macrophage-conditioned medium will increase incorporation in the presence of insulin but not in insulin-free media. Serum can substitute for macrophage-conditioned medium, but the two together show no additive or synergistic effect. The effect of estrogen on this system was determined, and results indicate that estrogen will perform the function of insulin, with an optimal concentration of 10(-10) to 10(-12) mol/L. Thus macrophage-conditioned medium appears to function as a competence growth factor, and estrogen (in appropriate concentrations) functions as a progression growth factor.