The nonsteroidal anti-inflammatory drugs are widely used in the United States and are a frequent cause of cutaneous reactions. Since December 1980, dermatologists have reported 135 of these drug reactions to a specialty-based Adverse Drug Reaction Reporting System. Reactions to piroxicam were most frequently reported; the majority of reactions to this drug were vesiculobullous and occurred most often in sun-exposed areas. Other reactions to nonsteroidal anti-inflammatory drugs not previously recognized include serum sickness, exfoliative erythroderma, and photosensitivity associated with sulindac; toxic epidermal necrolysis was reported with tolmetin, zomepirac sodium, and piroxicam. Fixed drug eruptions were noted with ibuprofen and naproxen, and photosensitivity was reported with sulindac and indomethacin. These findings illustrate the usefulness of a specialty-based system for spontaneous reporting of new and serious adverse reactions to drugs.