The objective of this study was to elucidate the mechanism(s) responsible for increases in the concentrations of basic drugs in cardiac blood of bodies in a supine position during early-stages postmortem. The concentrations of basic drugs in cardiac blood and other fluids and tissues of three individuals who had used one or more basic drugs were examined. The results were compared with those obtained in experiments using rabbits. In the first case, autopsy of whom was performed approximately 12 h after death, methamphetamine was detected and its concentrations were in the order: lung ≫ pulmonary venous blood > blood in the left cardiac chambers (left cardiac blood) ≫ pulmonary arterial blood > blood in the right cardiac chambers (right cardiac blood). In the second case, autopsy of whom was performed approximately 9 h after death, methamphetamine and morphine were detected and their concentrations in the left cardiac blood were roughly twice those in the right cardiac blood. The methamphetamine and morphine concentrations in the lung were 2 to 4 times higher than those in cardiac blood samples. In the third case, autopsy of whom was performed approximately 2.5 days after death, the pulmonary veins and arteries were filled with chicken fat clots. Toxicological examination revealed the presence of four basic drugs: methamphetamine, amitriptyline, nortriptyline and promethazine. Their concentrations in the lung were 5 to 300 times higher than those in cardiac blood, but postmortem increases in the concentrations of these drugs in the cardiac blood were not observed. In the animal experiments, rabbits were given 5 mg/kg methamphetamine intravenously or 20 mg/kg amitriptyline subcutaneously and sacrificed 20 min or 1 h later, respectively. The carcasses were left in a supine position at the ambient temperature for 6 h after or without ligation of the large vessels around the heart. For the groups with ligated vessels, the mean ratios of the drug concentrations in both left and right cardiac blood samples 6 to 0 h postmortem were about 1, whereas in those without ligated vessels, these ratios were about 2 and 1, respectively. The order of the methamphetamine and amitriptyline concentrations in blood and tissue samples were roughly: lungs > myocardium and pulmonary venous blood > cardiac blood, inferior vena caval blood and liver. Our results demonstrate that when bodies are in a supine position, (1) basic drugs in the lungs diffuse rapidly postmortem into the left cardiac chambers via the pulmonary venous blood rather than simply diffusing across concentration gradients, and (2) basic drugs in the myocardium contribute little to the increases in their concentrations in cardiac blood during the early postmortem period.