Widely used to study hepatic drug metabolism, antipyrine rapidly distributes in total body water. Antipyrine distribution was studied in seven lactating women. Duration of lactation ranged from 2 to 19 mo. In all subjects the drug was rapidly absorbed; in five women peak concentrations were attained in milk and saliva by 1 hr and in the other two women by 3 hr (first point at which collections were made). In two women in whom antipyrine was measured at 10-min intervals during the first hour, peak concentrations in both milk and saliva were attained by 10 min after antipyrine. The time course for antipyrine disappearance from milk paralleled that from saliva for each subject. Antipyrine half-life (t1/2) varied from 5.6 to 20.3 hr for saliva (mean +/- SD = 11.5 +/- 4.8) and from 5.7 to 21.7 hr for milk (mean +/- SD = 11.6 +/- 5.4). In the two women with the shortest salivary antipyrine t1/2 (5.6 and 7.5 hr), antipyrine was readministered many months later, after they had stopped lactating. The salivary antipyrine t1/2 rose from 5.6 to 13.3 hr in one subject and from 7.5 to 14.6 hr in the other. The corresponding decrease in antipyrine clearance was 0.93 to 0.55 and 1.41 to 0.60 ml/min/kg. This observation suggests that in some subjects lactation may influence drug metabolism. The amount of antipyrine available to each nursing infant was estimated by assuming the the infant nursed 3 ounces every 4 hr for 24 hr after maternal antipyrine administration. The amount of antipyrine available to the nursing infant was calculated to range from 3.0 to 11.1 mg (mean +/- SD = 6.4 +/- 2.9 mg) or from 0.25% to 1.07% (mean +/- SD = 0.59 +/- 0.29%) of the maternal dose.