OBJECTIVE: To investigate the possibility of direct effects of metformin on ovarian steroidogenesis. DESIGN: Cultured ovarian cells. SETTING: Academic research environment. PATIENT(S): Women undergoing bilateral salpingoophorectomy for benign gynecological disease. MAIN OUTCOME MEASURE(S): Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium. RESULT(S): The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude. CONCLUSION(S): These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).