Six subjects taking isotretinoin were studied, none of whom had clinical or phototest evidence of photosensitivity. Of nine subjects taking etretinate, one had convincing clinical photosensitivity consisting of a burning erythema on sunlight exposure. His phototesting results showed a marked abnormality from 300 +/- 5 nm to 365 +/- 30 nm which returned close to normal limits within one month of stopping therapy. Although clinically normal, another subject taking etretinate had similar phototest evidence of abnormal photosensitivity. In vitro photohaemolysis studies demonstrated that tretinoin (all-trans-retinoic acid) and isotretinoin have a potential, while etretinate has none. However, the major metabolite of etretinate (Ro 10-1670) had a phototoxic potential greater than that of tretinoin. The apparently low incidence of photosensitivity suggests that an idiosyncrasy is responsible, perhaps due to a disorder of pharmacokinetics or metabolism. Clinical cases should use appropriate photoprotection against UVB and UVA wavebands.