Using a radioimmunoassay specific for α-melanocyte-stimulating hormone (α-MSH), significant levels of immunoreactivity were detected in a range of murine and human melanoma cell lines, including a series of ras-transfected melanocytes. The levels found in the melanoma cell lines tested varied, and overall were higher than in non-melanoma cell lines assayed for comparison. Furthermore the highest levels of immunoreactivity measured tended to be in the least differentiated and most metastatic melanoma lines. High performance liquid chromatography showed a peak of immunoreactivity which co-migrated with a desacetyl α-MSH standard. Additional unidentified components of immunoreactivity were found, including a high molecular weight form revealed by Sephadex- G50 gel exclusion. These may represent bound α-MSH or fragments of the proopiomelanocortin precursor having in common the C-terminus epitope recognised by the antibody. In view of the known effects of α-MSH on anchorage independent growth and metastasis of melanoma cells, our findings raise the possibility that MSH peptides may have an autocrine role in the growth and progression of melanoma. However, further characterisation of the immunore-active species is required to determine whether these represent biologically active forms. © 1990 S. Karger AG, Basel.