Valorphin, an endogenous opioid-like hemoglobin fragment, is cytotoxic for L929 and K562 tumor cells in 10 - 7 -10 - 1 3 M concentration range. Because cytolytic effects induced by valorphin in K562 cells are inhibited by naloxone, opioid receptors should be involved in induction of valorphin-mediated tumor cell death. Three distinct cytolytic processes, differing in the onset time and the development time, take place with K562 cells within 10-18 h of incubation with valorphin. All three processes are not associated with apoptotic mechanism of cell death.