['A subset of drug-allergic patients show a marked propensity to react against several, chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs). The pathogenesis of such multiple drug reactions is unclear. Approximately 30% of patients with chronic idiopathic urticaria, a condition frequently characterized by autoreactivity on autologous serum skin test (ASST), experience flares of hives after taking chemically unrelated NSAIDs.', 'To detect whether a clinically unapparent autoreactivity may represent the nonspecific mechanism facilitating drug-induced histamine release in patients with a history of urticaria/angioedema induced by several, chemically unrelated NSAIDs.', 'Thirty-six adults with a history of acute NSAID-induced urticaria (22 with multiple NSAID sensitivity [MNS]; 14 with single NSAID sensitivity [SNS]; and 20 atopic controls without a history of drug allergy) underwent ASST. Sera from 14 MNS and 4 SNS subjects (all ASST-positive) underwent histamine release assay with basophils from normal donors. Sera from five MNS patients were tested on autologous basophils as well.', 'Twenty of 22 (91%) MNS subjects versus 5 of 14 (36%) SNS subjects were positive on ASST (P < 0.01). No atopic control was ASST-positive. Sera from 4 of 14 (29%) MNS patients versus 0/4 SNS subjects (P = NS) induced significant histamine release from basophils of normal donors. The use of autologous basophils did not significantly change these results.'] Is autoreactivity highly prevalent in patients with multiple intolerances to NSAIDs?