We determined the chemotherapeutic susceptibility of normal human granulocyte progenitor cells (CFU-C) and acute myelogenous leukemia cells (HL-60) in co-culture. Nucleated bone marrow cells and HL-60 cells were mixed in 0.3% agar containing McCoy's 5A medium, fetal bovine serum, human placenta-conditioned medium, and various concentrations of chemotherapeutic agents. They were incubated in 5% humidified CO2 at 37 degrees C for 8-10 days. CFU-C and HL-60 colonies were differentiated morphologically. The formation of CFU-C was progressively inhibited with the increasing number of HL-60 cells, whereas the presence or absence of bone marrow cells did not influence the number of HL-60 colonies. In separate culture, HL-60 cells were more sensitive to vincristine than were CFU-C cells. In co-culture, however, the CFU-C became more sensitive to vincristine than in the separate culture. Similarly, co-culture CFU-C were more sensitive to daunorubicin than in separate culture. These data indicate that HL-60 leukemic cells exert inhibitory effects on normal bone marrow CFU-C; in such an inhibited state, normal bone marrow is more susceptible to certain chemotherapeutic agents.