In this study, we tried to define in vitro interactions of two antitumor agents that have different sites and different mechanisms of action. Vinblastine (VLB) in combination with human recombinant interferon-alpha A/D (rHuIFN-alpha A/D) and in combination with murine recombinant interferon-gamma (rMuIFN-gamma) was studied. The effect of the combination was determined with cell growth kinetics assay on B-16 melanoma and the interaction defined by means of Spector's formula. Both the combination of rHuIFN-alpha A/D with VLB and the combination of rMuIFN-gamma with VLB synergistically inhibited cell growth in vitro. There was a positive biochemical modulation between the two drugs, but it is still unknown whether it occurred at the level of uptake into the cell, metabolism within the cell or egress from the cell.