The effect of anticonvulsant therapy on early morning concentration of cortisol in saliva and plasma was assessed in a group of epileptic patients receiving regular phenytoin medication and the results compared with those obtained from a group of normal subjects not receiving drug therapy. Values of cortisol in matched samples of plasma (331 +/- 23 nmol l-1, mean +/- s.e. mean, n = 6) and saliva (11.4 +/- 0.9 nmol l-1, mean +/- s.e. mean, n = 9) provided by epileptics did not differ significantly from those in the plasma (334 +/- 41 nmol l-1, mean +/- s.e. mean) and saliva (12.0 +/- 2.0 nmol-1, mean +/- s.e. mean) of healthy volunteers (n = 12). Six anticonvulsant-treated epileptics, together with six age and sex matched normal volunteers, each received intravenous dexamethasone (1 mg h-1) to determine the half-life of cortisol in plasma and saliva. In the anticonvulsant-treated group, the half-life of cortisol in plasma (73 +/- 5 min, mean +/- s.e. mean) and saliva (83 +/- 5 min, mean +/- s.e. mean) was reduced significantly (P less than 0.01 plasma, P less than 0.05 saliva) from that observed in healthy volunteers. In patients, the half life of cortisol and antipyrine showed a significant correlation (r2 = 0.75, P less than 0.05 plasma, r2 = 0.71, P less than 0.05 saliva). The antipyrine half-life in saliva was reduced significantly (P less than 0.02) and the antipyrine clearance rate, increased significantly (P less than 0.005) in the treated epileptic group, reflecting drug-induced microsomal enzyme production.(ABSTRACT TRUNCATED AT 250 WORDS)