Addition of prostaglandin E2 (PGE2) significantly altered the cellular composition of murine long-term bone marrow cultures. After 4--5 weeks of culture, increased cellularity in the suspension phase was observed in all cultures containing prostaglandin. These suspension cells contained markedly higher proportions of differentiated neutrophils than did cells cultured in the absence of PGE2. Granulocyte-macrophage progenitor cell levels in the suspension layer were increased 3--20 fold after five weeks in prostaglandin-containing cultures compared with control cultures. Fewer cells comprised the adherent layer in cultures containing prostaglandin. The number of macrophages in this layer was reduced 3--8 fold in these cultures compared with control cultures, while the number of granulocytes was increased 2--3 fold. The progenitor cells biased toward macrophage development were selectively inhibited in the cultures with PGE2. There was no significant effect of PGE2 on pluripotent stem cell levels or on the longevity of the cultures. It is concluded that excessive monopoiesis in bone marrow may be limited by PGE2 without influencing either stem cell maintenance or the development of other marrow-derived cell types.