The in vitro effect of sintamil, as a modulator alone and in combination with hydroxyurea (HU), on cytotoxicity was studied in 16 cases of human chronic myeloid leukemia (CML). We investigated the cytotoxicity of the drugs as a function of the exposure dose (HU, 10(-4) M; sintamil, 10 micrograms/ml) and the exposure time (1 h) to the agent. Cytotoxicity was evaluated as the inhibition of incorporation of [3H-methyl]thymidine in the nucleic acids of CML cells. Cytotoxicity of HU was greatly enhanced (P less than 0.001) by 1 h exposure of the CML cells to sintamil. The present data indicate that sintamil potentiates the cytotoxic activity of HU in CML cells.