The antitumor efficacy of calusterone, 200 mg/day by mouth, against objectively progressing advanced breast cancer was evaluated by the Cooperative Breast Cancer Group criteria in 117 women. In 41, calusterone was the first treatment for advanced breast cancer, in 49 it was given as secondary steroidal therapy, and in 27 it followed cytotoxic chemotherapy. Part of the study included comparison by the double-blind technique of calusterone in 23 women with Δ1-testololactone, 1,000 mg/day by mouth, in 25 similar patients randomly distributed for site of most significant metastasis and for age with respect to the menopause. Calusterone produced objective regressions lasting an average of 9.8 months in 51% of patients in whom it was primary or secondary hormonal therapy, but in only 19% of patients with previous cytotoxic chemotherapy. In the last group, regressions lasted only 6 months. Calusterone was equally effective in women with or without visceral metastasis, in all age groups, and in castration failures. In the double-blind study, calusterone produced regressions in 52% and Δ1-testololactone in 32% of patients. In the crossover, patients who had not responded to calusterone also failed to respond to Δ1-testololactone, while 33% of Δ1-testololactone failures or responders obtained regression on calusterone therapy. Calusterone is a weak androgen, and, like other 17α-alkylated steroids, produces nausea in 28 % of patients and BSP retention almost uniformly. There was no cholestatic jaundice or hepatocellular damage. Nausea was usually transient, but of sufficient severity in five patients to necessitate termination of therapy. Unlike other androgens, calusterone causes no rise in hematocrit, but a striking increase in the platelet count and a slight rise in the white blood cell count. By the rigorous criteria of the Cooperative Breast Cancer Group, calusterone is the most effective antitumor steroid thus far identified in a statistically adequate sample.