Summary:A phase Ia‐Ib study was undertaken to treat melanoma patients with a constant dose of the anti‐GD3monoclonal antibody, R24, in combination with increasing dose levels of recombinant interferon‐&agr; (rHuIFN&agr;‐2a). Fifteen patients were treated on days 1‐5 and 8‐12 with a continuous 6‐h i.v. infusion of R24 (8 mg/m2) and escalating i.m. doses of rHuIFN&agr;‐2a. Peripheral blood lymphocytes were obtained at multiple times before and during treatment and monitored for changes in lymphocyte subpopulations and changes in natural killer and antibody‐dependent cellular toxicity functional activity. There were no consistent changes in most immune parameters; however, there was a decrease from pretreatment levels in the suppressor T cell (CD8+, CD11b+) subset and a dose‐dependent decrease in the helper/inducer (CD4+, Leu‐8+) T cell subset. The peak serum concentration of R24 was reached on day 5 of the study and was 9.4 &mgr;g/ml. During the second week of treatment, peak serum levels of R24 fell to <4 &mgr;g/ml. This finding was related to the development of human antimouse antibody, which would be detected as early as day 8 of the study. Binding of mouse Ig (R24) within the tumor bed was observed in 5 of 12 biopsy specimens. The maximal tolerated dose of the combination was doselevel IV, in which patients received 8 mg/m2of R24 and 50 × 106units of rHuIFN&agr;‐2a on days 1‐5 and 8‐12 of treatment.