Objectives.The authors assess the costs associated with treatment of dyspepsia with histamine2antagonists versus without availability of over-the-counter (OTC).Methods.A cost analysis was performed using a decision-analysis model. Patients with an initial episode of dyspepsia were studied. The model includes costs associated with consumption of OTC and prescription (Rx) medications for dyspepsia, physician visits and associated diagnostic testing, time spent for physician visits and diagnostic tests, and hospitalization costs.Results.The model is sensitive to the relative cost of histamine2antagonists when purchased Rx or OTC, as well as to the efficacy of these drugs in relieving dyspeptic symptoms. For patients with nonulcer dyspepsia (the largest group of likely consumers), the model demonstrates a cost savings if the OTC cost of the medication is slightly less than one third the Rx cost. Costs are similar whether or not histamine2antagonists are available OTC. If the symptom relief efficacies of histamine2antagonists are equivalent whether purchased by prescription only or OTC, then the health-care expenditures for a typical patient with dyspepsia are $204 for OTC availability and $203 for Rx-only use. Viewing costs from the perspective of a managed-care organization, expenditures for an episode of dyspepsia are $149 regardless of whether or not histamine2antagonists are available OTC. Restricting the analysis to patients with underlying nonulcer dyspepsia yields similar results. Variation of numerous assumptions and probabilities other than histamine antagonist cost and efficacy, including costs associated with physician visits and diagnostic tests, and the likelihood of seeking medical care, do not substantially affect the results of the model.Conclusions.Health-care costs associated with initial treatment of dyspepsia are similar regardless of the availability of histamine2antagonists OTC. This is due largely to the similar efficacy of these drugs compared with antacids and the predicted increase in diagnostic testing that may result if a patient visits a physician after failure to achieve symptom relief with OTC use of histamine2antagonists.