Twenty-three aspirin (acetylsalicylic acid)-sensitive patients are reported. This sensitivity in patients with asthma occurred especially in middle-aged, white, atopic females having nasal polyps or chronic sinusitis, and blood eosinophilia. The course of these patients did not differ from that of the asthmatic patient without aspirin sensitivity. In studies of possible causative immune mechanisms, evidence of the antigenicity of aspiryl chloride was demonstrated in guinea pigs and in sensitized rabbits using passive cutaneous anaphylaxis, acute systemic anaphylaxis, microprecipitation, passive hemagglutination, and the lymphocyte transformation techniques. The same methods, with aspirin, aspiryl chloride, salicylic acid, and aspirin-altered human serum albumin as antigens, failed to demonstrate any consistent evidence for an immunological reaction in aspirin-sensitive asthmatic patients, in patients with rheumatoid arthritis who were receiving aspirin, and in normal individuals not taking it. The pertinent literature is reviewed.