The effect of a low estrogen oral contraceptive (OC) on glucocorticoid levels in plasma and saliva as well as glucocorticoid binding was studied in 23 healthy women using 30 μg ethinyl estradiol (EE2) + 150 μg desogestrel (Marvelon®) (II). Fifteen healthy females with normal menses served as controls (I). Blood and salivary samples were taken between 9.00 and 9.30 a.m. on the 18th day of menstrual or pill cycle. Assay accuracy had been optimised by applying extraction and chromatographic purification before radioimmunoassay (RIA) of cortisol and cortisone in both plasma and salivary samples. Free steroid assays were performed by applying the same procedure to equilibrium dialysates obtained after dialysing plasma against an equal volume of buffer, instead of measuring tracer distribution. Corticosteroid Binding Globulin (CBG) was measured by a commercial RIA. As expected, CBG as well as plasma total cortisol were elevated in the pill group. Interestingly both plasma free and salivary cortisol were higher than in controls (free cortisol I: 18.0 ± 7.95 nmol/l; II: 32.3 ± 9.03 nmol/l; salivary cortisol I: 9.2 ± 3.88 nmol/l; II: 18.8 ± 6.92 nmol/l. Salivary cortisol closely parallelled plasma free cortisol both within and between the groups, though at a much lower level (about 50%). Free cortisone was slightly lower in the pill group (I: 10.8 ± 2.55 nmol/l; II: 8.5 ± 1.86 nmol/lf) whereas salivary cortisone was 2.3 (I) and 4.4 (II) times higher than plasma free cortisone and tended to follow the plasma free and salivary cortisol pattern, both within and between the study groups. These latter observations were taken as suggestive of the presence of 11β-hydroxysteroid dehydrogenase (11βHSD) in the salivary gland, converting part of the entering cortisol into cortisone. Nevertheless, salivary cortisol must be considered to reflect adequately the increased plasma free cortisol during OC-administration.