OBJECTIVES: To examine the frequency and nature of FDA regulatory actions against pharmaceutical companies for unsubstantiated or misleading economic and quality-of-life (QOL) claims. METHODS: Review of publicly-available FDA warning letters and notices of violation (n=566) sent to pharmaceutical companies between January 1997 and November 2001 for inappropriate promotional claims. A standard data collection form was developed to capture the frequency and type of violation and the medium in which violations were found. We classified economic violations into several categories (e.g., "unsupported comparative claim of effectiveness, safety or interchangeability," "claims of cost-savings when there are obvious additional costs that may affect cost savings," "implied claims of cost-savings to a broader audience than applicable"). QOL violations for false or misleading claims using the words improved 'quality of life' or 'patient well-being' were classified into the following categories: "lack of substantial evidence for QOL claims," "promoting QOL claims in investigational or unapproved drug," and "selective presentation of QOL information". RESULTS: 28 (4.9%) letters cited false and/or misleading economic claims. The most common economic violation was an economic claim containing an "unsupported comparative claim of effectiveness, safety or interchangeability" (n=14). 28 (4.9%) letters cited QOL violations (4 letters contained both economic and QOL violations). The most common QOL violation was "lack of substantial evidence for QOL claims" (n=15). Violations were found most frequently in brochures and on websites. CONCLUSIONS: A body of evidence is emerging that illustrates how the FDA is regulating promotional material containing misleading or unsubstantiated economic and QOL claims. Knowing what constitutes an economic or QOL violation remains unclear, because there are no formal guidelines about what constitutes a violation, nor what level of substantiating evidence is required. More guidance may be needed to ensure appropriate use in drug promotions.