A previously undetected population of macrophage progenitor cells with high proliferative potential (HPP-CFC; an average of 5 x 10(4) cells/colony) in nutrient agar cultures has been demonstrated in post-fluorouracil (FU) and fluorouracil plus endotoxin (FUEt) treated and normal mouse bone marrow, using a combination of colony-stimulating factors, pregnant uterus extract (PMUE) plus human spleen-conditioned medium (HUSPCM). Neither PMUE nor HUSPCM alone stimulated colony formation by the HPP-CFC. The incidences of HPP-CFC were 1 in 2380 nucleated cells in normal marrow, 1 in 380 for 10-day post-FU, and 1 in 118 in 8-day post-FUEt marrow cells. HPP-CFC were only depleted to 57% of normal at 2 days after FU treatment, whereas the cells responsive to PMUE alone (low proliferative potential, LPP-CFC) were depleted to 1.2%, indicating a marked difference in cycling status of the respective types of progenitor cells.