We determined the serum levels of macrophage colony-stimulating factor (M-CSF) in 441 women with gynecologic diseases to evaluate its role as a marker for gynecologic malignancy. Serum M-CSF levels were above the normal baseline level of 1,056 U/ml in 64% (56/88) of patients with ovarian cancer, 27% (16/60) of those with cervical cancer, and 25% (15/61) of those with endometrial cancer. M-CSF was significantly elevated in the serum of patients with advanced as compared with early stage cancer (stage I) of the ovary (p < 0.01), cervix (p < 0.05), and endometrium (p < 0.05). Only 5.6% of the patients with benign ovarian tumors and 7.0% of those with endometrial cysts had serum levels of M-CSF that exceeded 1,056 U/ml. M-CSF was localized in the glandular epithelial cells as well as in the stromal macrophages and the endothelial cells of the ovarian cancers. M-CSF thus appeared to be a marker with high specificity for ovarian cancer.