We evaluated the effect of commonly used pharmaceutical estrogens and zeranol, an estrogenic growth-promoting agent used in livestock, on progesterone (P) production by cultures of highly differentiated porcine granulosa cells (GC). The compounds were added to GC cultures over a dose range of 10(-8) to 10(-5) M with P and cell protein measured after 24 h. P production was suppressed by estradiol (minimal suppressive dose: 10(-7) M; maximal suppression to 11% of control), ethinyl estradiol (10(-7) M, 15%), diethylstilbestrol (10(-5) M, 72%), clomiphene citrate (10(-6) M, 30%), nafoxidine (10(-7) M, 33%), tamoxifen (10(-6) M, 37%), and zeranol (10(-5) M, 83%). P production was not suppressed by mestranol. GC protein was suppressed by estradiol, ethinyl estradiol, nafoxidine, and zeranol. These data suggest that synthetic estrogens have the potential to suppress luteal P production by a mechanism unrelated to the usual measures of estrogenicity.