Aims Various nonsteroidal anti-inflammatory drugs are known to increase the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis. The relationship between salicylate treatment and these conditions is not known. Methods A case-control study was conducted in four countries in Europe from 1989 to 1995. Results Among 373 cases and 1720 controls, the multivariate relative risk estimate for any salicylate use in the previous week was 1.3 (95% confidence interval, 0.8-2.2); no statistically significant elevations were observed for single ingredient preparations or for salicylate-containing combination products. Conclusions Acetylsalicylic acid and other salicylates are not associated with a measurable increase in the risk of these rare but severe reactions.