We have developed a simple, direct radioimmunoassay for progesterone in saliva. The correlation coefficient (r) between the direct assay and an extraction procedure was 0.92 (n = 65, P < 0.001), and the correlation between concurrent serum and salivary progesterone concentrations in the luteal phases of menstrual cycles of 48 women was 0.75 (P < 0.001). Whereas certain polystyrene and polyethylene vials and tubes were found to bind and remove up to 87% of the progesterone from saliva, other plastic and glass surfaces were satisfactory for the procedure. Intraassay and interassay CVs from values greater than 300 pmol/L were 12.0 and 12.4%, respectively. The assay sensitivity was 48 pmol/L. Collection of saliva is a more convenient and less invasive technique for frequent sample collection than phlebotomy, and is useful for monitoring ovulation and assessment of luteal function in women clinically.