The effects of prostaglandin E1 (PGE1) on leukemia colony formation were investigated in seven cases of acute nonlymphocytic leukemia. In contrast to the almost constant results observed for normal myeloid colony formation, in patients there were apparent individual variations. Strong inhibition of colony formation by PGE1 was observed in three cases. In one case, enhancement rather than inhibition was observed. These in vitro inhibitory or stimulatory effects of PGE1 were not related to the degree of the in vivo proliferation of leukemia cells. Morphologic analysis of colonies revealed that preferential inhibition of monocytic colony formation by PGE1, characteristic of normal bone marrow cultures, was not always observed in leukemia cell cultures. These abnormal responses to PGE1 suggest that the proliferation and differentiation of leukemic progenitor cells are regulated in a different way from normal hemopoiesis.