Recombinant interferon alpha (rIFN-alpha) has shown antitumor activity in metastatic malignant melanoma both as single-agent therapy and in combination with chemotherapeutic agents. As a single agent, rIFN-alpha yields an objective response rate of approximately 15%, which is comparable with other biologic agents, such as recombinant interleukin-2 (rIL-2) and single-agent chemotherapy. The most effective application of rIFN-alpha to the treatment of metastatic melanoma seems to be as a component of drug regimens that combine rIFN-alpha with rIL-2 or with combination chemotherapy regimens. The combination of rIFN-alpha with rIL-2 appears to have greater antitumor activity than either agent alone. Likewise, rIFN-alpha may potentiate the antitumor activity of combination chemotherapy regimens. Chemoimmunotherapy using dual biologic agents is currently the most promising therapy for metastatic melanoma with objective response rates of more than 50%. The greatest success of chemoimmunotherapy is its ability to produce durable complete remission in approximately 10% of treated patients. These regimens produce long-term remissions and offer hope to patients with advanced melanoma.