Monoclonal antibodies (mAb) were selected for differential binding to sections of freshly frozen biopsy material of human malignant melanomas and their precursor lesions, the melanocytic nevi. Both melanomas and normal nevi expressed human Ia-like antigens, transferrin receptor and the transferrin-related molecule p97. In contrast, only 1 nevus of 21 tested expressed both glycoprotein gp75, defined by mAb 15.75, and protein p89, defined by mAb P3.58, whereas 12 of 15 melanomas tested expressed both antigens. mAb P3.58 reacted with one additional melanoma and one nevus. The expression of these two molecules therefore appears to be correlated with the appearance of the malignant phenotype of melanocytes.