Transgenic mice carrying the RET oncogene under the control of the metallothionein promoter exhibit severe pigmentation of the whole skin and melanocytic tumors. The genetic background influences melanoma development in RET mice; founder mice crossed with BALB/c mice show decreased incidence and increased latency of melanocytic tumors, whereas progeny of C57BL/6 mice show the opposite effect. Using partially congenic RET mice on a C57BL/6 genetic background (N3/RET mice), we studied genetic linkage in (N3/RETxBALB/c)xN3/RET backcross mice. We mapped three melanoma modifier loci, on chromosome 1 (Melm1 and Melm2) and chromosome 11 (Melm3), that are linked with early melanoma incidence and latency. Mapping of Melm loci and of five additional regions on chromosomes 6, 8, 9, 12, and 13 indicated allelic imbalance in N3/RET mice, with a significant excess of BALB/c alleles, suggesting the presence of additional putative melanoma modifier loci on these chromosomes.