The possible connection between changes in splenic phagocytic activity and increase of splenic macrophage/granulocyte progenitors (colony forming cells - CFC) in mice was studied. Intravenous administration of increasing amounts of colloidal carbon, or sheep red blood cells (SRBC), 3 hours prior to injection of 10(7) 51Cr labeled SRBC caused a decrease in phagocytic activity in liver and an increase in spleen. Under the same experimental conditions, injection 10(7) unlabeled SRBC induced an increase of splenic CFC. Increase in splenic phagocytic activity and in numbers of splenic CFC showed a linear relationship. Both activities depended on the amounts of colloidal carbon or SRBC injected prior to injection of 10(7) SRBC. These findings suggest that mature macrophages may participate in controlling the increase in number of splenic CFC after injection of particulate substances such as SRBC or colloidal carbon. It was also found that increase of splenic CFC, under the experimental conditions described, was not affected by neonatal thymectomy.