We have evaluated the in vitro leukocyte histamine release tests for the diagnosis of allergy to muscle relaxant drugs in 40 patients (Group A) and a control group of 44 subjects with negative leukocyte histamine release (Group B). Non-IgE dependent histamine release, expressed as a percentage of the total blood histamine, was 3.94% +/- 0.49 in Group B. The upper limit of positivity was estimated to be 5% (mean + 2 SD). Leukocyte histamine release tests were positive in 65% of the patients from Group A. The concordance between LHR and QAS-RIA was 64%. The maximal histamine release was observed at dilutions of 10(-2)-10(-4) in 20 of the 26 positive cases. The maximal histamine release was 43.8% +/- 23.3. The spontaneous histamine release was as low as 1.7% +/- 1.1. Cross-reactivity among the 5 different muscle relaxant drugs has been investigated and compared by intradermal testing. The muscle relaxant drugs which gave the lower skin reaction (M2) and the drug responsible for shock (M1) were selected for the study of in vitro leukocyte histamine release. Of 20 M2. All of the 10 cases had negative ID tests with M2. Three of these patients subsequently underwent general anesthesia with the muscle relaxant chosen as harmless (M2) without any clinical reaction.