Using a model of uncomplicated burn injury in mice, we assayed the bone marrow and splenic production of granulocytes and macrophages after burn injury. The effects of burn size and burn wound excision and closure were studied. Using an in vitro quantitative clonal culture technique for granulocyte/macrophage progenitor cells (GM-CFC), myeloid precursors were directly assayed. Burns of a 10% body surface area were equal to burns of larger magnitude for effects on marrow and splenic granulocyte/macrophage production. The total peripheral blood leukocyte and lymphocyte counts were depressed at days 1 and 4 postburn but were elevated at days 8 and 12. Granulocytes, however, remained significantly increased at days 8 and 12. The bone marrow response to burning showed an initial depression in marrow cellularity on day 1 with return to normal values by days 8 and 12. The numbers of GM-CFC were significantly elevated on days 4-12 with a near threefold increase in the number of GM-CFC 12 days following burn injury. The splenic response to burn injury was characterized by a decrease in the splenic index on day 1 but then a persistent increase at days 8 and 12. Total splenic cellularity was depressed on day 1 but significantly increased at days 8 and 12. The total number of splenic GM-CFC was increased on days 4-12 with a 100-fold increase on day 8. The immediate or delayed excision of the burn wound did not alter marrow or splenic response to burning. We conclude that following a cutaneous injury there is a marked alteration in the generation of the phagocytic cells of the granulocyte and macrophage series and that this response is secondary to the wounding process.