Twenty-six patients with metastatic breast cancer who had previously responded to one or more endocrine therapies participated in a clinical trial of the combination of trilostane and hydrocortisone for subsequent disease progression. Of these, one patient achieved complete remission (4%), and five had partial response (19%). The median time to progression from initiation of therapy for responding patients was six months (range: 4 - 32 + months). Major toxicities included nausea/vomiting (16 patients), facial flushing (14), abdominal cramping (11), and oral paresthesia (10). Therapy was discontinued in four patients (15%) because of drug intolerance. Fourteen patients who failed trilostane were treated with aminoglutethimide and hydrocortisone. Six patients showed objective response (PR + MR). These data show that trilostane and hydrocortisone in combination can produce an objective response in a significant fraction of patients and that the combination has a different spectrum of toxicity from aminoglutethimide/hydrocortisone. A small number of patients crossed over to aminoglutethimide showed a few objective responses, suggesting a partial lack of cross-resistance between the two antiadrenal drugs.