The absolute bioavailability of orally administered caffeine was investigated in 10 healthy adult male volunteers, aged 18.8 to 30.0 years. The subjects were administered a 5 mg/kg dose of caffeine as either an aqueous oral solution or an intravenous infusion, on separate occasions about 1 week apart, in a randomized crossover fashion. Plasma samples were collected over the 24-h period following each dose and assayed for their caffeine content using a high-performance liquid chromatographic technique. The oral absorption was very rapid, reaching a peak (Tp) plasma concentration after 29.8 +/- 8.1 min (mean +/- SEM). In addition, the variation in the maximum plasma concentration (Cmax) was low, 10.0 +/- 1.0 micrograms/ml. The absolute bioavailability was assessed by comparing the areas under the plasma concentration vs. time curves for the intravenous and oral doses of caffeine. The rapid absorption resulted in essentially complete bioavailability of the oral caffeine, F(%) = 108.3 +/- 3.6%. The caffeine plasma half-lives varied from 2.7 to 9.9 h, indicating substantial inter-subject variability in its elimination.