The in vitro influence of clomiphene citrate on the incorporation of acetate-1-14C into progesterone by slices of human corpora lutea was studied in 10 experiments using the reverse isotopic dilution technique for the isolation and purification of radioactive progesterone, followed in most instances by crystallization to constant specific activity. As a clear-cut and reproducible result, the formation of progesterone from labelled acetate was considerably diminished in the presence of clomiphene citrate independent of whether the tissues originated from the menstrual cycle or from normal as well as ectopic pregnancies. This inhibitory effect on the biosynthesis of progesterone was intensified by increasing the concentration of clomiphene in the medium. It was demonstrable after 13.3 minutes of incubation as well as after 6 hours. No obvious interference of clomiphene with the stimulating action of HCG on steroidogenesis was found. These findings point to a direct action of clomiphene on the ovary which might also have some bearing on the mode of action of clomiphene in vivo.