To evaluate the effect of puberty on antipyrine metabolism, we measured antipyrine pharmacokinetics in 17 healthy subjects aged 6-21 years. The subjects received a single oral dose of antipyrine, 18 mg/kg. Salivary antipyrine levels were determined 3, 6, 9, 12 and 24 h after dosing. Age, weight, body surface area and Tanner stage were highly intercorrelated. Volume of distribution (liters) was highly correlated with all of these factors. The weight-corrected clearance of antipyrine declined significantly with age (r = 0.55, p less than 0.025). Patients were classified as immature and other based on serum hormone levels (immature = females with serum estradiol less than 25 pg/ml and males with serum testosterone less than 25 ng/dl). The uncorrected antipyrine clearance was significantly lower in the immature group (mean +/- SD 22.65 +/- 6.04 ml/min) than in others (mean +/- SD 41.30 +/- 13.26; p less than 0.01). This difference disappeared when the weight-corrected antipyrine clearance was compared for these two groups. The change in uncorrected antipyrine clearance with sexual maturation appeared to be due to increased body size, probably related to the adolescent growth spurt.