SummaryThere is an increasing interest in measuring human plasma histamine levels in various clinical conditions. A variety of 'old' and newly developed techniques are applied to meet this demand. However, the discrepancy between reported reference values for histamine in human plasma measured using this variety of techniques, suggests the existence of a certain degree of inaccuracy and imprecision. We therefore organized an external quality control study on the reliability of current histamine determinations in European laboratories. Three lyophilized plasma quality control samples, in duplicate, covering the normal and pathological range of histamine concentrations {0-45 nmol/l), two different aqueous histamine standard samples and one solvent sample were sent to 10 laboratories for the analysis of their histamine content. The following methods were used: gas chromatography-mass spectrometry (« = 2), enzymatic single isotopic assay («= 1), fiuorometric-fluoroenzymatic assay (« = 3). radioimmunoassay (« = 3) and high performance liquid chromatography {n = 2). The study was performed and evaluated according to the approved recommendations (1983) ofthe International Federation of Clinical Chemistry (IFCC). The target values ±s.d. ofthe three plasma samples were: 39-5±4-6 nmol/l (CV=ll-6%), 2 3 + 2-2 nmo!/l (CV-96%) and 8-9+1-5 nmol/l (CV=17%), respectively. The target values +s.d. ofthe two aqueous samples were: 0-9± 1-1 nmol/l (CV= 120%; true value: 0 00 nmol/l) and 10 2±0-5nmol/l(CV=5 3%; true value: 10 Onmol/l), respectively. A Youden plot oftwo unrelated plasma samples in the pathological range defined 7/11 results as accurate and precise. The Youden plot of the two unrelated aqueous samples only defined 6/11 results as accurate and precise. In general, estimating histamine concentrations within the normal range seemed to be the most difficult part of measuring histamine in human plasma samples. It is suggested to define reference standards, methods and laboratories for plasma histamine determinations.