Caffeine (300 mg) was given orally to nine healthy subjects at 10:00 AM (day trial) or at 10:00 PM (night trial) using a crossover design. Saliva was obtained at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of caffeine. Urine was collected for 8 hours after caffeine dosing. Caffeine clearances in saliva during the day trial were not different from those in the night trial. No significant difference was observed in urinary molar ratios of metabolites (AFMU + 1X + 1U/17U) between the two trials. These data suggest that caffeine clearances in saliva do not vary with its administration time. Since caffeine clearances in plasma are reflected in the urinary ratios of caffeine metabolites, its clearance in plasma might also not be altered by the time of dosing.