Abstract A sensitive, specific and accurate radioimmunoassay of progesterone in human saliva is described. The assay had a sensitivity of 8 pg/tube and blanks were negligible. The intra- and inter-assay coefficients of variation were 5.2 and 9.4%, respectively. The mean recovery from 60 samples was 93.2 ± 6.3%. Results obtained from nine healthy, normally menstruating women showed that salivary progesterone rose from the 4th day before ovulation to a mean peak (± SD) of 1.14 ± 0.17 ng/ml on the 8th day after ovulation, followed by a gradual decline. Correlation of salivary and simultaneously obtained plasma progesterone levels was good ( r = 0.47; P < 0.001), although the maximum percent increase in salivary progesterone was more than 10 times greater than that of plasma progesterone. Salivary progesterone is thought to reflect the unbound fraction of plasma progesterone and this non-invasive technique can be used for serial investigations in which frequent samplings are required.