Degenerative changes of human tumor cells or continuous cell lines occur when they are cocultured with human embryonic fibroblasts. The present study confirmed that the degenerative changes of the target cells were due to a factor secreted from the human fibroblast culture, because the culture supernatant of human fibroblast caused the same degenerative changes as those induced by the coculture. This factor was termed "tumor-degenerating factor" (TDF). TDF was produced in the fibroblast culture as early as the 1st day and increased gradually up to the 8th day. TDF induced the degenerative changes in human KB cells, HeLa cells, FL cells, and PLC/PRF/5 cells but not in human WiDr cells or in fibroblasts. Also, it did not induce the degenerative changes in various murine cells, bovine cells, rabbit cells, or monkey cells, suggesting that TDF has species specificity. Furthermore, human leukocyte interferon enhanced the activity of TDF. TDF with the specific activity of 2.9 U/mg protein was purified by several chromatographies. At a final recovery rate of 14.6%, the specific activity was increased to 9,010 U/mg protein. Its molecular weight was estimated about 26,500-30,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. TDF was relatively stable to heat treatment.