The purpose of this study is to test the hypothesis that rapidly dissolving immediate-release (IR) solid oral products containing a highly soluble and highly permeable drug [biopharmaceutical classification system (BCS) class I] are bioequivalent under fed conditions. Metoprolol and propranolol (BCS class I) as well as hydrochlorothiazide (BCS class III) were selected as model drugs. The relative bioavailability of two FDA approved (Orange Book AB rating) solid oral dosage forms of metoprolol and propranolol/hydrochlorothiazide (combination tablets) was evaluated in human volunteers under fed conditions using a two-way crossover design. Equal numbers of male and female volunteers were recruited, and racial and/or ethnic minorities were not excluded. The plasma concentrations of metoprolol, propranolol, and hydrochlorothiazide were determined using validated high-performance liquid chromatography (HPLC) methods. Eighteen subjects completed the metoprolol study while 17 subjects completed the propranolol/hydrochlorothiazide combination tablet study. In the metoprolol study, the 90% confidence intervals of Cmax and AUC(inf) were 98-118% and 92-115%, respectively. For propranolol, the 90% confidence intervals of Cmax and AUC(inf) were 91-121% and 89-117%, and for hydrochlorothiazide, the 90% confidence intervals for Cmax and AUC(inf) were 96-107% and 97-106%, respectively. These study results appear to support the hypothesis that rapidly dissolving IR solid oral products containing a BCS class I drug are likely to be bioequivalent under fed conditions. In addition, BCS class III drugs may have the potential to be bioequivalent under fed conditions.