Chronic treatment of mice with morphine selectively abrogates the terminal differentiation of com mitted bone marrow progenitor cells to form macrophage colony forming units. To understand the molecular mechanisms involved in morphine-mediated suppression of myeloid cell differentiation, we investigated the use of a macrophage cell line, Bac 1.2F5. In vitro proliferation of this cell line is dependent on the exogenous supply of macrophage colony stimulating factor. Treatment of Bac 1.2FS cells in vitro with morphine showed a dose-dependent inhibition of proliferation which was associated with morphological changes. Characterization of the binding site revealed that the binding site for morphine on these cells is different from the classical opioid receptors described in the brain. In addition to the putative novel class of morphine receptors, Bac 1.2F5 cells also expressed the delta opioid receptors as determined by RT-PCR analyses. These studies show that Bac 1.2F5 cells are suitable for the molecular characterization of opioid effects on the proliferation and differentiation of myeloid progenitor cells.