The renal clearance of caffeine was calculated following both oral and intravenous doses of 5 mg/kg caffeine in eight young and eight elderly, healthy human volunteers. There was a highly statistically significant positive correlation (P less than 0.001) between the renal clearance of both unbound (CLRu) and total (CLR) caffeine and the mean urine flow rate over the 24-hour period after dosing. Attempted correlations of CLRu and CLR with hydrogen ion concentration or creatinine clearance and of creatinine clearance with urine flow rate all proved to be statistically nonsignificant. It is suggested that the control of salt and fluid intake and other factors affecting urine flow rate may be a worthwhile endeavor in pharmacokinetic studies of drugs with properties similar to caffeine.