Eight patients with Colorado tick fever were studied to determine whether alterations in the production of granulopoietic stimulatory or inhibitory factors (or both) could be found in association with the leukopenic state of the disease. The studies demonstrate that in the patients with Colorado tick fever the mononuclear cell production of colony-stimulating factor is decreased and that there is an increase in circulating inhibitory factors in the serum of such patients. The depressed mononuclear cell colony-stimulating activity does not appear to be reversible by addition of either endotoxin or normal human serum. Characterization of these serum inhibitory factors may facilitate understanding of leukopenia in human disease.