The prognosis for most patients with metastatic melanoma is poor, as the median survival is only 7 months. Phase II trials of chemoimmunotherapy have, however, reported response rates of 40% to 70% and prolonged disease-free survival in small subgroups of patients. Most chemoimmunotherapy trials have used high doses of recombinant interleukin-2 (rIL-2) and recombinant interferon alpha (rIFN-alpha) that produce significant toxicity and require prolonged hospitalization to manage side effects. To develop a treatment regimen for metastatic melanoma that would minimize costly hospitalization, we initiated a phase II trial of outpatient chemoimmunotherapy. Patients were treated with monthly cycles of intravenous carmustine, dacarbazine, cisplatin, and tamoxifen plus self-administered subcutaneous rIL-2 and rIFN-alpha as outpatients. To date, 32 patients have received 94 cycles of therapy. The most common toxicity was nausea and vomiting. Hospitalization for the management of toxicity was required in only seven cycles (7%). Thirty patients have been assessed for clinical response. The overall response rate was 43% (13% complete and 30% partial response). This phase II trial has established a tolerable regimen of outpatient chemoimmunotherapy, which has shown significant antitumor activity.