Since L-dopa (L-3,4-dihydroxyphenylalanine) has been shown to possess a selective toxicity for melanoma cells both in vitro and in vivo, we have examined the combined effect of L-dopa and radiation on human melanoma cells. It was found that the combined use of L-dopa potentiated the radiation cytotoxicity to HMV-I human melanoma cells, compared with the response seen in non-melanoma HeLa S3 cells. In HMV-I cells during their exponential phase, L-dopa decreased the shoulder width of the radiation survival curve significantly. In addition, L-dopa significantly inhibited the repair of potentially lethal damage (PLD) in HMV-I cells during their plateau phase. When the distributions of the G1, S, and G2-M cells were measured 24 h after combined L-dopa and radiation treatment, there was significant increase in the accumulation of cells in the G2-M phase of the cell cycle, compared to cells that received either L-dopa or radiation treatment only.