We compared the endoscopic effects and pharmacokinetic profiles of an experimental buccal formulation of piroxicam to oral capsules in an attempt to determine whether nonsteroidal antiinflammatory drug-induced gastropathy is due to a local or systemic effect. Ten healthy subjects received 20 mg piroxicam daily in a double-blind, randomized, crossover, placebo-controlled study. Upper endoscopies were performed at the baseline and at the end of each 2-week dosing arm of the study. Pharmacokinetic data obtained included serum and gastric piroxicam concentrations and serum 5'-hydroxypiroxicam metabolite concentrations after the first dose and 2 weeks of dosing. No differences in endoscopy scores or patient symptom scores were noted between the two dosage forms after 2 weeks of dosing. Pharmacokinetic data of piroxicam and the metabolite revealed that the buccal formulation may not have been absorbed exclusively from the buccal mucosa.