Aspirin anhydride (ASAN) has been found to be a frequent contaminant of commercial acetylsalicylic acid (ASA) preparations. ASAN is a highly immunogenic substance susceptible to form protein conjugates in vitro, to induce the formation of anti-aspiryl antibodies and of contact hypersensitivity to ASAN in guinea pigs and rabbits. Commercial ASA samples varied greatly in their capacity to induce hypersensitivity to ASAN under standardized conditions in guinea pigs. As demonstrated with various types of aspiryl-protein conjugates, antibodies induced by ASAN and detected by passive cutaneous anaphylaxis are mostly of aspiryl specificity. Antibodies of similar specificity have been detected in patients ingesting aspirin. A few patients presenting a reliable history of generalized urticaria and acute angioneurotic edema after ingestion of aspirin showed skin hypersensitivity to aspirylpolylysine. The possible significance of contamination of acetylsalicylic acid preparations by aspirin anhydride in the development of untoward reactions to aspirin is discussed.