In the present study, we treated a total of 62 patients with advanced renal cell carcinoma with high-dose tamoxifen (100 mg/m2/day). Patients were treated in the outpatient setting, and were evaluated 8-12 weeks after initiation of therapy or sooner, when clinical disease progression was evident; a total of 15 patients were seen at short regular intervals for evaluation of clinical and laboratory parameters. Of these 62 patients, 59 were evaluable for treatment response, survival and systemic toxicity. One partial remission was achieved (1.7%; 95% confidence interval, 0.04-9.09%), response duration was 3 months. 10 patients presented with stable disease, for a median duration of 4.0 months, and 48 patients exhibited disease progression upon and after therapy. Systemic toxicity was significant; severe fatigue occurred in 5% of patients, and moderate anaemia, dyspnea, alopecia and malaise in almost 20% of patients. Antineoplastic efficacy of tamoxifen at this dosage in this cohort of patients was at best marginal and well in the range associated with the occurrence of spontaneous remissions. Toxicity was substantial, and it was not balanced by therapeutic benefit. This is consistent with the known lack of therapeutic efficacy of endocrine therapy in advanced renal cell carcinoma.