This study describes the expression pattern in the human uteroplacental unit of c-fms, the proto-oncogene that encodes the receptor for colony-stimulating factor-1. Quantitative mRNA analysis showed that c-fms mRNA expression in placental tissues was lowest in first trimester samples and highest at the end of pregnancy. Expression of c-fms mRNA was also high in first trimester endometrium and term chorion. Although c-fms mRNA was approximately 3.7 kb in size on northern blots of all placental, endometrial, and chorion preparations, trophoblast-specific transcription of c-fms exon 1 was confirmed by primer-directed amplification of reverse-transcribed total RNA. Immunohistochemistry using both polyclonal and monoclonal anti-c-fms protein antibodies showed that c-fms protein was expressed over the entire trophoblastic area during the first trimester but became progressively restricted to the villous syncytiotrophoblast as pregnancy advanced. Of particular interest was the high level of c-fms protein expression in the intermediate trophoblasts of the villous sprouts during first trimester. The synthesis of c-fms protein was also detected in glandular epithelial cells and decidual cells of first trimester endometrium and in the extra-villous trophoblastic layer of the chorion.