Melanotic hamster malignant melanoma (MM1) is a transplantable, locally invasive tumor which metastasizes widely in syngeneic hosts. We have established three clones, HM1, HM3, and HM4 of the original MM1 line in culture. Inoculation (s.c.) into 4- to 5-week-old male athymic mice produced highly vascular, melanotic, locally invasive tumors in 100% of mice inoculated with a latency of 4-7 days. Karyotype analysis of HM cells revealed modal chromosome numbers of 39-41 (43% HM1), 43 (22% HM3), and 44-47 (61% HM4). Sixty-one % of HM1 cells were hypodiploid, 4% diploid, and 5% hyperdiploid. HM1, -3, and -4 cells also exhibited aneuploidy, endoreduplication, translocational exchanges, additions, deletions, dicentromeric and ring chromosomes, and double minutes although not all cells exhibited all abnormalities. Initial metastasis was to regional lymph nodes with eventual progression to lung and liver. Mice inoculated with HM1, -3, and -4 cells were dead with metastatic disease within 57, 63, and 64 days, respectively, following s.c. inoculation (5 X 10(5) cells) when the mice were 90-100 days old. Mortality rate was highest in line HM3 with 50% of the mice dead within 33 days postinoculation. Metastatic potential of HM1 and HM3 cells rose significantly when successive generations of HM1 and HM3 cells cultured from isolated lung metastasis were reinoculated. Metastasis to lymph nodes and liver was not observed with increasing passage generations of lung metastasis. Our observations provide evidence that hamster melanomas are clonally heterogenous, locally invasive, and exhibit rapid growth and metastasis following s.c. inoculation into adult athymic mice. Transplantable melanotic hamster melanoma cells also exhibit a significant preferential metastasis to lung following culture and sequential reinoculation of lung metastasis in athymic mice. As such, they appear to provide a reproducible model of metastasis in an immunocompromised host.