The efficacy of trioxifene mesylate, a new antiestrogen, in the management of advanced breast cancer was evaluated in 69 patients. Fifty-two patients were randomly allocated to dose schedules of 5 mg, 10 mg, and 20 mg orally twice daily. There were five complete responders (10%), 22 partial responders (42%), and 9 patients (17%) with no change in disease. The median time to progression was 12 months (range, 4-27+). Positive estrogen receptor status, long disease-free interval, and low tumor burden (with fewer sites of disease) correlated with higher response rates. Higher doses did not result in better responses. Another group of 17 patients who responded to prior tamoxifen administration, upon failure, were treated with trioxifene. Two (12%) had partial remission with time to progression of 3 and 10 months, respectively. Side effects were mild and generally well-tolerated, with hot flashes being most common (20%). These results suggest that trioxifene mesylate is an active agent, and has similar therapeutic efficacy and toxicity compared with those reported for tamoxifen. In a small fraction of patients treated after tamoxifen therapy was received, objective response was also observed. This observation requires further evaluation.