L-DOPA, the product of enzymatic hydroxylation of L-tyrosine, is released by melanotic melanoma cells in vivo and in vitro. Here we report that DOPA at pharmacologically relevant micromolar doses dramatically inhibits the stimulation of DNA synthesis by lipopolysaccharide and concanavalin A in murine splenocytes and human lymphocytes, having little or no effect on unstimulated (control) lymphocytes or proliferating fibroblasts. Therefore we propose that melanogenically active melanoma cells can inhibit the host's immune response via the release of DOPA and/or its oxidation products.