In an earlier study we confirmed the usefulness of intradermal skin tests and histamine release in diagnosis of patients reactive to muscle relaxants, and we suggested an IgE-mediated reaction rather than an idiosyncratic mechanism. In a later study, we studied the relationship between (Formula: see text) that is one of the muscle relaxants producing the most frequent adverse reactions under anesthesia. Histamine release was measured in five patients with increasing concentrations of suxamethonium in the presence or absence of human serum albumin in Tris buffer. Suxamethonium by itself without any carrier in the buffer could, in vitro, act as a true allergen on target leukocytes in the sensitized patients' group. Acetylcholine (20 and 200 micrograms/ml) did not induce significant histamine release in five patients with positive histamine release in the presence of suxamethonium. Preincubation of leukocytes from 11 patients for 30 min with 20 and 200 micrograms of acetylcholine in Tris albumin CA++ Mg++ buffer decreased the histamine release induced by suxamethonium (10 micrograms/ml); mean maximal histamine release of 46% +/- 4.2 was reduced to 31.4 +/- 5.8 and 7% +/- 4 (p less than 0.001), respectively. However, in eight control subjects similar concentrations of acetylcholine did not change the maximal histamine release induced by anti-IgE (0.2 micrograms/ml). In the same way acetylcholine did not modify histamine release induced by Dermatophagoides pteronyssinus extract (1/10,000 w/v) in six patients allergic to this allergen. This study suggests that suxamethonium acts as a true allergen and that acetylcholine or one of its metabolites may act as a hapten inhibitor in the model of histamine release induced by suxamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)