Our experience with the combination of dacarbazine, carmustine, cisplatin with and without tamoxifen is reported. In our initial study, with all 4 drugs, we had an overall response rate of 50% with a complete response rate of 15%. Due to a high incidence of deep venous thrombosis and the lack of effectiveness of tamoxifen as a single agent, we deleted tamoxifen from the regimen and treated another 20 patients. Surprisingly, the response rate decreased to 10%. We then re-incorporated tamoxifen into the regimen and treated 25 additional patients. In this third group of patients we experienced an objective response rate of 52% with a complete response rate of 8%. Overall, 65 patients have been treated: 45 with and 20 without tamoxifen. Twenty-three (51%) patients treated with tamoxifen have responded, with 5 (11%) patients achieving a complete response. Only 2 (10%) patients treated without tamoxifen have responded. Despite the improvement in the response rate, a corresponding increase in survival has not been seen. Patients treated with tamoxifen had a mean survival of 10.8 (SD 13.6) months compared with a mean survival of 9.8 (SD 7.3) months for those treated without tamoxifen. The absence of survival advantage for the tamoxifen-treated patients may be due to early failure in the central nervous system. In 48% of the responding tamoxifen-treated patients, the first site of failure was the central nervous system, while systemic disease was still responding.