Pregnant FDA-strain Osborne-Mendel rats were administered repeated doses of caffeine by oral intubation (gavage) and by administration in the drinking water (ad libitum sipping). When [1-methyl-14C]caffeine was administered at a dosage of 80 mg per kg per day by ad libitum sipping on days 12 to 15 of gestation, the amounts of radioactivity in blood were variable; the highest level on day 12 was 0.2% of the dose per ml of blood. The highest blood level of caffeine observed during a 24-h sampling period averaged 5.7 micrograms ml-1. When [14C]caffeine was administered by gavage at a dosage of 80 mg kg-1 on day 12, the blood level of radioactivity reached a peak of 0.4% of the dose per ml of blood and declined rapidly thereafter. The highest amount of caffeine observed in blood averaged 63.1 micrograms ml-1, 1 h after gavage. The overall blood elimination half-life of radioactivity in pregnant rats treated by gavage was 2.6 h, and the half-life of caffeine in blood was 1.7 h. The levels of radioactivity in the fetus and maternal muscle per unit weight were comparable after each method of administration. A comparison of autopsy results from both groups indicated that resorptions were increased when compared with rats that did not receive caffeine; this effect was more marked in the gavage group than in the ad libitum sipping group. Ectrodactyly was observed only in offspring of the gavage group. The incidences of ectrodactyly or resorptions did not appear to be directly related to nutrition or fluid intake.