Cimetidine pharmacokinetics and metabolism were studied in 2 full-term and 1 premature neonates. All infants demonstrated the capacity to eliminate cimetidine via both metabolic and renal routes. The half-life of cimetidine ranged from 3.4 to 2.1 h, and decreased as total body clearance increased. These alterations in pharmacokinetics were felt to represent developmental and maturational differences, primarily in renal function. In contrast to the 60% routinely seen in adults, approximately 90% of the administered dose was recovered in the urine of the full-term infants as cimetidine and its known metabolites. Cimetidine sulfoxide and hydroxymethyl cimetidine were detected in the serum and urine of 2 patients, and the elimination half-life of these metabolites was two- to threefold longer than values seen for cimetidine. During multiple dosing of cimetidine, significant accumulation of cimetidine metabolites may be expected. The reported dose of 15-20 mg/kg/day is adequate in full-term neonates, however, it appears that premature infants and those with renal dysfunction may require lower dosing rates.