A prospective controlled clinical trial was conducted on changes in plasma histamine and catecholamine levels during 5 standard operations. This communication, as the first part of the trial, deals only with the feasibility of such a trial and the changes in plasma histamine levels. Elevated histamine concentrations corresponding to histamine-release responses of greater than 1 ng/ml occurred in 8 of 25 operations. In an explorative analysis these responses were associated with distinct phases of anaesthesia or the surgical procedure. Blood transfusion carried the risk of infusion of "free histamine" into the patient--especially when administered under pressure. Since during operations "free histamine" enters the circulation with a rather high incidence and may cause harmful effects, premedication with H1-+H2-receptor antagonists seems worth consideration.