We compared in vitro the cytotoxic activity of vinorelbine (VRB) (Navelbine, 5'-nor-anhydro-vinblastine) a novel Vinca alkaloid, with that of vinblastine (VBL) vincristine (VCR) and vindesine (VDS). Five continuous human melanoma cell lines (C32, G361, StMl11a, StMl12d and StMl14a) and a new line WHMel 1, were used in this study. In growth-inhibition assays, VDS and VRB exhibited comparable cytotoxicity against the C32 and G361 melanoma lines; the effect being dose- and time-dependent. VRB appeared less inhibitory compared to VDS in the lowest concentrations (0.1-1 nM). The same activity was observed with 0.1-1 microM. These drugs exhibited comparable growth inhibition at clinically achievable doses. The MTT assay was used to compare VBL, VCR, VDS, and VRB. Overall IC50 values (concentration required to reduce viability by 50%) ranged from 1 pM to 10 nM. The reduction in cell viability with VRB was similar to that observed with the reference drugs in four out of five lines tested by this method. However a trend was observed for IC50 values to be lower with VBL and VDS. In clonogenic assays (StMl11a, StMl12d and StMl14a lines, 1 h exposure) VRB and VDS produced the same reduction in survival. Survival curves were exponential followed by a terminal plateau. IC50 values ranged from 60 nM to 70 nM. Our results indicate that VRB has in vitro activity against six melanoma lines with differing phenotypic characteristics.