Histamine concentrations in canine whole blood and plasma were determined under several pharmacological, pathophysiological, and clinical conditions using fluorometric methods.The specificity of the assay for whole-blood histamine was investigated by comparing 3 purification procedures for the isolation of histamine from whole blood including butanol extraction (Shore), ion-exchange chromatography on Dowex 50 W-X 8, and the combination of these 2 methods (Lorenz). Histamine in whole blood was identified in analytical and preparative samples by fluorescence spectra, thin-layer chromatography, degradation by diamine oxidase from pig kidney and inactivation by histamine methyltransferase from guinea-pig brain as well as by biological tests on the isolated guinea-pig ileum. Since butanol extraction resulted in significantly higher 'histamine' values than the other two purification procedures, ionexchange chromatography on Dowex 50 was recommended as the method of choice for the specific determination of histamine in doffs whole blood.Normal values of histamine concentrations in canine plasma were tentatively estimated. They depended on the time between pretreatment of the animals (anaesthesia, operation) and the collection of blood and showed an approximately logarithmic normal distribution. The median, the lower/upper quartiles and the range of the plasma histamine levels obtained 30 minutes after the end of pretreatment were 0.2, 0-0.4 and 0-1.2 ng/ml, respectively. Nearly 50 % of the values were zero (below 0.1 ng according to the sensitivity of the method), only 1 ~ of them exceeded slightly 1 ng/ml. Thus histamine release by drugs or by other medical treatments was only stated, when plasma histamine levels exceeded 1 ng/ml and decreased in a way to give an elimination carve of approximately first-order kinetics (Bateman function).Histamine concentrations in dog's whole blood showed approximately a logarithmic normal distribution. The median, lower/upper quartiles and range were 47, 34/75 and 13-209 ng/ml respectively.