The injection of either viable B16 melanoma cells, killed B16 cells, or B16 cell products increased the incidence of melanomas in C57Bl/6J mice inoculated with a threshold dose of B16 cells. In all cases the effect was seen whether the facilitating injection was at a site distant from the challenge inoculum or at the same site. Facilitation was seen with B16 cells and products both from in vivo tumors and from tissue culture. However, cells detached from tissue culture flasks with trypsin no longer had facilitating activity. Facilitating activity was found in concentrated cultured supernatants centrifuged at 100,000 X g for 1.5 hr and dialyzed. No activity was detected in the less than 10,000 mol wt fraction. Facilitation was not associated with a change in the time of tumor appearance nor with enhanced growth of B16 cells in culture.