Bacterial lipopolysaccharides (LPS) enhance both production of colony-stimulating factors (CSF) and proliferation of mononuclear phagocytes in vivo. The present study was undertaken to determine whether the effects of LPS on CSF-dependent monopoiesis are due solely to enhanced production of CSF or also to direct effects of LPS on the responding progenitor cell. Addition of LPS to CSF-stimulated macrophage populations had different effects, depending upon the concentration of CSF in the cultures. In the presence of optimal to supraoptimal concentrations of CSF, LPS at doses >/=0.01 mug/ml inhibited macrophage colony formation. This inhibitory activity was not due to cytotoxicity of the LPS and was not mediated through prostaglandin synthesis. In the presence of suboptimal concentrations of CSF, minute concentrations of LPS (10(-7) mug/ml) significantly enhanced macrophage colony formation. Both effects of LPS (inhibition and enhancement) appeared to be properties of lipid A since neither effect was noted with cells from LPS-resistant C3H/HeJ mice, whereas both effects could be neutralized by the addition of the antibiotic polymyxin B, which binds to the lipid A portion of LPS. These results suggest that the effects of LPS on monopoiesis in vivo may not be due solely to its capacity to stimulate production of CSF. Rather, LPS may be involved in stimulating monopoiesis both indirectly through stimulation of CSF production and by its effects on the CSF-responsive progenitor cell.