Adverse reactions to drugs require that their mechanisms be elucidated, particularly when anaphylaxis is suspected. Early diagnosis can be achieved by plasma histamine measurements. Unfortunately, the short plasma half-life of histamine and the difficulties in handling the sample usually preclude this measurement, although a sensitive radioimmunologic kit is routinely available. It has been recently suggested that mast cell tryptase, a component of the mast cell granules, could provide an alternative to histamine determination. We have measured plasma histamine and tryptase in 19 patients who developed possible anaphylactoid reactions to anesthetic or other drugs. Eight patients had increased values for both histamine and tryptase. In 4 a muscle relaxant drug was proved responsible for the reaction. Six patients had normal levels for both substances. In each case, the clinical signs of anaphylaxis were moderate. Two patients had normal histamine and high tryptase concentrations, due to late sampling (greater than 5 h). In 2 other patients, histamine was high, with normal tryptase: in 1, muscle relaxant allergy was further demonstrated. Tryptase half-life was equal to 90 min in 3 patients. At least 15 min was necessary to reach the peak level when the responsible drug was administered intravenously. The best time for measuring tryptase was 1-2 h after the reaction (not greater than 6 h), whereas for histamine it was 10 min to 1 h. We conclude that measurement of plasma tryptase along with measurement of plasma histamine may aid in diagnosis of anaphylaxis.