Interferon-alpha 2 (IFN-alpha 2) produced by recombinant DNA technology and purified to homogeneity, was assessed for effects on plasma lipids and lipoprotein composition in 10 patients with metastatic malignant melanoma. Patients received 30 X 10(6) U/m2 IFN intravenously for 5 consecutive days every 3 weeks. Plasma cholesterol concentrations were significantly decreased after 3 days of IFN administration (171 +/- 37 mg/dl, mean +/- SD) when compared with pretreatment concentrations (211 +/- 28 mg/dl, p less than 0.05). Approximately 34% of the decrease in plasma cholesterol concentration was contributed by high-density lipoprotein (HDL). Significant decreases in plasma HDL cholesterol (44 +/- 8 to 34 +/- 7 mg/dl, p less than 0.05) and apolipoprotein A-1 concentrations (124 +/- 14 to 95 +/- 17 mg/dl, p less than 0.05) occurred. Although decreases in low-density lipoprotein (LDL) cholesterol concentrations contributed to the majority of the total decrease observed in plasma cholesterol, IFN did not alter the cholesterol-to-protein ratio of the LDL. When IFN-alpha 2 was discontinued, alterations in plasma lipoproteins returned to pretreatment levels. Plasma triglyceride concentrations were not influenced by IFN treatment nor did administration of IFN decrease very-low-density lipoprotein (VLDL). The overall effect of recombinant (r) IFN-alpha 2 on lipid composition was to reduce LDL and HDL without alteration of VLDL or triglycerides.