The aim of this study was to determine whether femoral arterio-venous plasma concentration differences (AVD) of amitriptyline exist during acute intoxication in man. All patients studied were comatose and were divided into a control group who had two successive blood samples drawn from the same vessel and a study group who had samples drawn from the femoral artery and vein simultaneously. Serial plasma concentrations of amitriptyline were measured by gas liquid chromatography. In each group the differences were assessed by means of the Wilcoxon matched pairs test. In the control group (n = 13) there were no differences (T = 31, n = 12). In the study group (n = 24) the AVD were significantly different (T = 52, n = 23). For amitriptyline, the arterial or venous origin of blood samples for toxicological studies must be stated.