Skin photosensitivity is a side-effect reported for several non-steroidal anti-inflammatory drugs (NSAID). In vitro studies have revealed phototoxic properties in a majority of these compounds with a preponderance for derivatives of propionic acid. Fourteen NSAIDs, the majority commercial preparations in clinical use, have been assayed by the mouse tail technique for in vivo phototoxicity evaluation. Intraperitoneal single doses in the range 12.5-200 mg/kg were given in combination with UVA irradiation for 5 h (total dose 54 J/cm2). The phototoxic reaction was measured 24 h later as the wet weight increase of tail tissue over non-irradiated, drug-treated controls. Four out of 9 propionic acid derivatives were phototoxic: tiaprofenic acid, carprofen, benoxaprofen and naproxen. Among NSAID compounds of other chemical structure only diclofenac and diflunisal were weakly photoactive. The propionic acid derivatives fenoprofen, flurbiprofen, ibuprofen, indoprofen and ketoprofen were negative, as were azapropazone, piroxicam and sulindac among the unrelated compounds. Phototoxicity is one important aspect of NSAID photosensitization. It is advisable to perform predictive studies including in vivo models, such as the mouse tail technique, before new NSAIDs are introduced on the market.