The gene product of the viral proto-oncogene v-fms, associated with the feline sarcoma virus (SM-FeSV), is a glycoprotein of 170 kd with associated tyrosine kinase activity. The murine c-fms proto-oncogene produces a similar glycoprotein of 165 kd and has been implicated as a similar, if not identical, molecule to the cell surface receptor of the hematopoietic growth factor CSF-1. Employing a v-fms probe in an in situ hybridization assay we examined the expression of c-fms transcripts in a population of purified granulocyte-macrophage progenitor cells (CFU-GM). Using this approach, which requires only 10-20 thousand cells, we demonstrate that 53% of the cells in the purified CFU-GM containing fraction (FR-28) express c-fms transcripts. In the presence of natural purified CSF-1, 51% +/- 3% of FR-28 cells form colonies or clusters in a semi-solid culture assay system. 94% of the colonies and clusters stimulated by CSF-1 were morphologically macrophage in nature. In addition, 84% +/- 4% of FR-28 cells formed colonies and clusters when stimulated with pokeweed mitogen spleen cell conditioned medium (PWMSCM) in a similar in vitro assay (35% granulocyte, 29% macrophage and 39% mixed granulocyte/macrophage colonies). These results indicate there is a correlation between the responsiveness of CFU-GM progenitor cells to CSF-1 and the expression of c-fms RNA.