Twenty-four patients survived life-threatening clinical anaphylaxis due to anesthesia. In each case the diagnosis of anaphylaxis was confirmed and the responsible drug was found by intradermal testing. To determine whether the reactions were anaphylactic or anaphylactoid, serum from each patient was tested for reaginic activity using Prausnitz-Kustner (PK) testing in human subjects and monkeys and passive cutaneous anaphylaxis (PCA) testing at four and 24 hours in monkeys. Positive results of PCA testing at four hours were repeated with serum that had been heated to 56 C for two hours. Drugs used in testing were Althesin, thiopental, succinylcholine, gallamine, d-tubocurarine, and alcuronium. Vehicles and antioxidants were tested separately. Positive tests suggestive of the presence of reaginic antibodies occurred with sera from 15 patients who had had previous exposure to the drug. Nine patients had tests suggestive of IgE antibodies on first exposure, suggesting that cross-sensitivity may be a factor in such reactions to muscle relaxants. Two patients had positive tests for IgG antibodies. This is further evidence of the role of this mechanism in immediate allergy and demonstrates another mechanism by which anaphylaxis can occur without previous sensitization. Four patients had positive tests for IgE antibodies after previous exposure. It was concluded that it is not possible to determine the mechanism of anaphylaxis from a history of previous exposure.