The metabolic pathway of theophylline (T) was studied in 12 newborns, one young infant, six children, and three adult volunteers. T was injected IV, and blood and urine samples were assayed for T, caffeine (C), and their metabolites by a high-pressure liquid chromatography technique. We confirmed the methylation of T to C in newborn infants but not in older subjects. Demethylation of T to 3-methylxanthine was found in the young infant, in children, and in adults, but not in newborns. The major products excreted by neonates were T, 1-methyluric acid, and 1,3-dimethyluric acid. Children excreted a larger fraction of methyluric acids than adults. Renal and body clearance of T and C are reported and discussed in relation to the age.