Venlafaxine is a unique antidepressant currently under evaluation for treatment of various affective disorders. The pharmacokinetics and relative bioavailability of venlafaxine were evaluated in healthy volunteers after oral administration. The bioavailability of 50 mg of venlafaxine as a tablet relative to a solution was determined in a two-period randomized crossover study. The rate of absorption from the gastrointestinal tract was assessed by the time to peak plasma concentration (tmax), a model-dependent calculation of the first-order absorption rate constant, and a model-independent calculation of mean residence time. The extent of absorption was assessed by peak plasma concentration (Cmax) and area under the concentration-time curve (AUC). No statistically significant differences were observed between the two formulations for either the rate or extent of absorption. Similarly, systemic concentrations of the active O-demethylated metabolite did not significantly differ after administration of the two venlafaxine formulations. AUC ratios indicated that the relative bioavailabilities of the parent drug, and formulation of metabolite were approximately 98% and 92%, respectively, for the tablet versus the solution. A separate study was conducted to examine the influence of food on venlafaxine absorption from the 50-mg tablet. A standard, medium-fat breakfast eaten immediately before drug administration delayed the tmax of venlafaxine but did not affect Cmax or AUC. Therefore the tablet formulation of venlafaxine is bioequivalent to the oral solution, and the presence of food appears to decrease the rate but not the extent of absorption of venlafaxine from the tablet formulation.