The culture supernatant of human fibroblasts caused degenerative changes in the target cells. This tumor degenerating factor in the supernatant (TDF) appeared already on the 1st day of culture and increased gradually to the 8th day. TDF was effective on human KB, HeLa, FL and of hepatoma cells, but neither on murine L929, 3T3, SV-3T3 cells nor MDBK cells. Furthermore, TDF was not effective on human non-transformed cells, namely various human fibroblasts. Human leukocyte interferon (HuIFN-alpha) enhanced TDF production. The coculture of human fibroblasts with KB cells augmented TDF production.