In order to explore the potential oncostatic properties of the pineal hormone, melatonin, we have investigated its binding characteristics and functional effects in a human malignant melanoma (M-6) cell line. Binding studies in M-6 membranes showed the coexistence of 2-[125I]iodomelatonin binding sites with picomolar and nanomolar affinities. Guanine nucleotides caused conversion of all high-affinity sites to a low-affinity state without a change in binding capacity. Melatonin induced a marked concentration-dependent reduction in forskolin-stimulated cAMP accumulation in intact M-6 cells, indicating that it binds to a functional receptor in this cell line. The in vitro proliferation of M-6 cells was significantly inhibited by melatonin and its analogues 6-chloromelatonin, and 2-iodomelatonin, at concentrations ranging from 10(-9) to 10(-4) M, as demonstrated by cell counts and measurements of DNA content. These findings indicate that M-6 cells express functional receptors for melatonin which may be involved in mediating the antiproliferative effects of this hormone.