Postmenopausal patients with metastatic breast cancer were treated with aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA). Studying the interaction between the two drugs as far as plasma MPA and cortisol levels are concerned we observed a 50% decrease of plasma MPA levels after the addition of AG (P less than 0.005). With large interindividual differences in plasma MPA levels, a significant correlation with serum cortisol levels was found (P less than 0.001). It can be concluded that AG leads to a lowering of plasma MPA levels to such an extent that its adrenal suppressive effect may be diminished or even abrogated. In future trials of MPA with or without AG correlations between plasma MPA levels, serum cortisol levels and treatment response should be taken into account.