OBJECTIVE: To compare this switch with prior Rx-to-OTC switches and discuss its economic, clinical, and public health implications. METHODS: The FDA held meetings in May 2001 to determine if prescription (Rx) second-generation antihistamines (SGAs) should be sold over-the-counter (OTC). This meeting warranted much attention because a party other than drug manufacturers requested the switch, and SGAs' patents have not expired. Literature reviews of prior switches and allergic rhinitis (epidemiology and clinical management) were conducted. Microeconomic theories were used to examine economic implications of switching SGAs. RESULTS: Past experiences of switching drugs to OTC status (i.e., topical hydrocortisone, H2-blockers) have resulted in lower prices and greater consumer surplus and availability. It is unclear if similar conclusions can be drawn about SGAs, whose patent protection differentiates them from prior switches of patent-expired drugs. Predictions of the switch's economic consequences (i.e., pricing and social welfare) cannot be made without full knowledge of demand elasticity in the antihistamine (first- and second-generation) market. Additionally, a mandated switch prior to patent expiration may discourage research and development. From a clinical perspective, selling SGAs OTC may reduce physician intervention, leading to drug misuse and missed diagnoses of severe co-morbidities (e.g., asthma). From a public health perspective, if SGAs are removed from Rx formularies post-switch, patients could be responsible for total drug acquisition costs. This may diminish availability for financially vulnerable populations (i.e., Medicaid recipients). CONCLUSIONS: Selling SGAs OTC may increase availability and decrease the use of sedating antihistamines. However, the net impact of their switch remains unknown. The lack of generic competition implies prices for SGAs may not fall nor may social welfare improve. Cost-benefit analyses are needed to determine if benefits of the switch will outweigh costs of misdiagnoses and misuse. Lastly, the impact of the switch on vulnerable populations must also be explored.