The biodistribution of [1-(14)C]ethanol in rodents was examined to determine sites of concentration of ethanol or its metabolites that may contribute to its toxicological and pharmacokinetic characteristics. After i.v. administration of [1-(14)C]ethanol in mice, radioactivity showed a widespread distribution among body organs. Determination of the proportion of tissue radioactivity accounted for by volatile [1-(14)C]ethanol versus nonvolatile (14)C metabolites indicated that tissue radioactivity was mostly in the form of the latter, even as early as 5 min after injection, indicating a rapid metabolism of the radiolabeled ethanol to labeled metabolites. In a separate study, radioactivity was imaged using whole-body autoradiography after i.v. administration in rats. High levels of radioactivity were observed in the Harderian gland, preputial gland, and pancreas at 15 and 60 min after injection. High levels of radioactivity were also apparent at the later time point in the intestinal tract, indicating hepatobiliary excretion of radiolabeled metabolites. Moderate levels of radioactivity were present in the liver, lungs, salivary glands, bone marrow, and kidney cortex. In conclusion, after i.v. [(14)C]ethanol administration, radioactivity initially distributes widely among body organs but concentrates in specific tissues at subsequent time points. Especially notable in the current study was the high concentration of radioactivity accumulating in the pancreas. It is thus tempting to speculate that the well documented high incidence of pancreatic disease observed in human chronic alcoholism may be related to a propensity of this organ to accumulate ethanol and/or reactive ethanol metabolites.