Twenty-eight adults with a history of a generalized allergic reaction during anesthesia were investigated. The reactions were systemic in 23 adults, urticaria/angioedema in four, and bronchial obstruction in one adult. The study population and an additional 35 subjects with a history of use of thiopental during anesthesia but without reactions were investigated by methods including thiopental skin test, succinylcholine skin test, and IgE RAST for antibodies to thiopental, succinylcholine, or latex. Among the 28 patients with reactions, 17 had positive thiopental skin tests; 14/28 reactors and 1/35 of the control group had an IgE thiopental RAST value greater than 2 SD above the mean for control sera from ragweed-allergic subjects. The one control subject with a positive thiopental RAST also was the only control subject with a positive thiopental skin test. IgE succinylcholine RAST was negative in all 23 reactor sera tested. The IgE latex RAST was strongly positive in one reactor. In conclusion, evidence of allergy, particularly allergy to thiopental as a possible basis for the reactions, was obtained in greater than 50% of the patients who were investigated. No allergy to succinylcholine was found.