Abstract In this study, we estimated interstitial histamine concentrations in normal and malignant tissues after a single intravenous (i.v.) injection of 0.5 mg/kg histamine dihydrochloride in the rat. The microdialysis technique was used to collect interstitial fluid from subcutis, liver and a NGW adenocarcinoma. Histamine was absorbed with equal efficiency to all tissues (t1/2 AB 3.9–7.7 minutes) but maximum concentration (Cmax; nmol/l) of histamine was higher in liver (2388±357) than in subcutis (951±125) (p<0.01) and subcutaneous tumor (523±140) (p=0.01) and, moreover, Cmax in liver tumor (1752±326) was higher than in subcutaneous tumor (p=0.01). The t1/2 elimination was significantly longer in subcutis and subcutaneous tumor than in liver and liver tumor. Area under the curve (AUC; mmol-min/l) for histamine was significantly lower in subcutaneous tumor (9.8±2.3) than in liver (17.6±1.9) (p=0.03) and liver tumor (15.8±1.8) (p=0.03). Local tissue blood flow as assessed by the 14C-ethanol method was not significantly altered by the histamine administration. In conclusion, after an i.v. injection of histamine dihydrochloride a higher maximum concentration and AUC of histamine was reached in liver and liver tumor than in subcutaneous tissues.