Three markers of in vivo histamine release, i.e. plasma histamine and tryptase, and urinary methylhistamine, were assessed using sensitive radioimmunoassays in 18 patients who had experienced an adverse reaction to an anaesthetic agent. Controls were obtained from 35 patients following a general anaesthetic, which included a muscle relaxant, and who remained free from any adverse reaction. A first blood sample was obtained from all 18 patients a mean 25 +/- 26 min after the reaction, and a second one in thirteen a mean 120 +/- 65 min after the reaction. Ten patients had had a life-threatening reaction. Plasma histamine levels were increased in all these cases, and tryptase concentrations in 9 out of 10. Urinary methylhistamine rarely reached pathological levels (4 out of 10). Skin tests were positive in the four tested patients. Plasma histamine concentration was still high in 8 cases thirty minutes after the reaction, and remained increased for more than 2 h in two patients. Among the other eight patients with a moderate reaction, 3 had high histamine levels, with normal or weakly increased tryptase concentrations, and normal urinary methylhistamine. Two of these patients had positive skin tests. There were no abnormal findings in any of the investigations carried out in the other five patients, except for a slightly positive skin test to atracurium in one patient. Plasma histamine had a higher sensitivity than tryptase levels. Methylhistamine concentrations were only rarely of interest. There were no false positives with the three investigated markers.(ABSTRACT TRUNCATED AT 250 WORDS)