A radioimmunological method for measuring saliva cortisol was worked out. It includes one extraction and one radiocompetitive reaction with an anticortisol 3-CMO:BSA immunoserum. Frequent values for saliva cortisol were determined in various physiological and pathological conditions and compared to plasma cortisol values. In adult men, the mean concentrations at 8 a.m. and midnight were respectively 14.50 ± 7.10 and 1.40 ± 1.21 nmol/l (x ± SD). In untreated women, plasma and saliva cortisol levels were not significantly different from those measured in women taking estroprogestative drugs or in pregnant women. Following stimulation by synthetic β1-24 ACTH (Synacthen®), the saliva cortisol determined 90 min after the 8 a.m. sampling rose by over 500% whereas plasma cortisol only rose by 120%. Similarly the drop in 8 a.m. cortisol, which followed midnight administration of 1 mg of dexamethasone was larger for saliva than for plasma cortisol. In patients with adrenal hyperactivity the circadian rhythm disappeared from saliva cortisol and patients with deficient adrenal activity displayed drastically reduced levels for saliva cortisol. Saliva cortisol seems thus to be more helpful to diagnosis than plasma cortisol.