An analysis was made of fibroblastoid colony-forming units (CFUF) in spleens of mice treated with bacterial lipopolysaccharide (LPS). Increased CFUF numbers were observed on days 2, 3 and 4 after treatment with 10, 30 and 100 micrograms of LPS. The splenic CFUF accumulation occurred at the same time as spleen hemopoiesis increased, however, the CFUF returned to normal and subnormal numbers on day 5, while the spleen cellularity was still elevated on day 21 after LPS treatment. The mechanism of splenic CFUF accumulation appeared to involve CFUF migration via the blood from other sites of hemopoiesis rather than increased CFUF plating efficiency in vitro or enhanced CFUF proliferation. The results suggest a relationship between the LPS-induced fibroblastoid progenitor cell increase and a requirement for splenic microenvironments to support LPS-induced hemopoiesis.