Hypersensitivity adverse drug reactions are the most common serious adverse drug reactions to sulfonamide (sulfa) therapy. It has been demonstrated that reactive sulfa metabolites are important in the pathogenesis of these adverse reactions. Given the involvement of the immune system in these reactions, it has been suggested that drug haptens may be important in the pathogenesis of these reactions. In order to explore the role of drug haptens, sulfamethoxazole (SMX) -specific antibodies were raised in New Zealand white rabbits. Rabbits were immunized with SMX and adjavent and antibody harvested. Western blots were run using anti-rabbit primary and goat secondary antibodies to study samples from patients with adverse reactions to SMX-TMP and from control volunteers who were treated with a course of SMX-TMP. A 42-kd band was found on a Western blot from a child who had sustained an adverse reaction to SMX-TMP, but no similar bands were demonstrated using serum from two other patients who had had adverse reactions to SMX-TMP. No similar bands were found in the serum of 14 control volunteers who were treated with a course of SMX-TMP for 10 days, with samples being obtained at 0, 3, 7 and 14 days, despite the fact that the hydroxylamine of sulfamethoxazole was detected by HPLC in urine of these volunteers in concentrations from 3 ± 2% of the original sulfa dose. This suggests that sulfa-specific haptens may play a role in sulfa hypersensitivity reactions, but that this appears to be inconsistent; it also suggests that, during sulfa therapy among most patients, hapten formation is uncommon.