N-Methyl-4-phenylpyridinium ion (MPP+) was found to be accumulated in human melanoma cell lines, HMV-I and -II, which originate from human melanoma and differentiate into subclones, HMV-I and -II. HMV-II cells can produce a large amount of melanin, while the other cells produce less. After 3 day culture of these cells in the presence of 1-100 microM MPP+, MPP+ was accumulated in both types of cells and a much larger amount of MPP+ was accumulated in melanin-rich HMV-II cells than in HMV-I cells, even though the uptake velocity of MPP+ into both types of cells was almost the same. In addition, both types of cells could survive, even with MPP+ accumulation. Protein amounts, a non-specific enzyme, beta-galactosidase activity, and intracellular DOPA concentrations in both types of cells, were not affected by the presence of MPP+. These results suggest that MPP+ is accumulated in non-dopaminergic cells and the accumulation is enhanced by the presence of melanin.