Because Corynebacterium parvum has tumor-inhibitory properties and stimulates granulocyte-macrophage production, it may have clinical value in combination with chemotherapy. The leukopoietic effect of killed suspensions of C. parvum was studied in mice using the technique of in vitro clonal culture of hematopoietic cells. After C. parvum injection, there was a prompt, sustained elevation of serum colony-stimulating factor followed by an increase in granulocyte-macrophage precursor cells in the spleen and increases in blood mononuclear and granulocyte cells. Colony-stimulating factor production is suggested as a major mechanism of stimulation of granulocyte-macrophage proliferation by C. parvum. Since rapidly proliferating hematopoietic cells may have increased sensititity to cytotoxic agents, the details of hematopoietic stimulation by C. parvum may be critical in the sequential timing of combined C. parvum and chemotherapy treatment to obtain maximal tumor inhibition and minimal hematopoietic toxicity.