We have developed 8 peptide derivatives as potential MC1R antagonists and their inhibitory effects on ${alpha}$-MSH induced cell growth in cultured normal human melanocytes (NHM) were investigated. From these experiments, the two most potent peptide derivatives, 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_6NH_2$ (P 6) and 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_9NH_2$ (P 7) were selected for further studies. In ${alpha}$-MSH depleted NHM cells, we have found that the treatment with 1 ${mu}M$ of these two peptide derivatives, P 6 and P 7, inhibited the cell proliferation induced by the addition of 1 nM ${alpha}$- MSH by 70% and 72%, respectively. In NHM cells without previous ${alpha}$-MSH depletion, 1 ${mu}M$ treatment in the presence of 10 nM ${alpha}$-MSH resulted in 70% (P 6) and 80% (P 7) decrease in cell growth and 64% (P 6) and 71% (P 7) reduction in melanin synthesis, respectively. The peptide derivatives P 6 and P 7 were proved to have no apparent cytotoxicity and inhibited the elevation of intracellular cAMP concentration triggered by ${alpha}$-MSH. In conclusion, our data suggest that the peptide derivatives reported in this study, 5-phenylvaleric acid-(D)His-Arg-Trp-$(Lys)_6NH_2$ (P 6) and 5-phenylvaleric acid-(D)His- Arg-Trp-$(Lys)_9NH_2$ (P 7) strongly antagonize ${alpha}$-MSH, inhibit cell proliferation and melanin synthesis, and lower the intracellular cAMP concentration, hence have a promising potential as a novel skin lightening agent.