Estrogen receptors have been demonstrated in human hypernephroma (renal cell carcinoma). Antiestrogens have been demonstrated to have antitumor activity in animal models of this disease. A prospective trial of tamoxifen therapy was undertaken in 10 consecutive patients with unresectable hypernephroma. No major responses to tamoxifen were observed. A review of the literature on antiestrogen therapy for this tumor reveals 148 published cases of hypernephroma treated with tamoxifen or nafoxidine. The overall response rate was 7.4%. Antiestrogens appear to have little clinical usefulness in the treatment of advanced hypernephroma.