The influence of food intake and water deprivation on the absorption and toxicity of acetaminophen in mice. There is controversy concerning the toxic influence of food in acetaminophen intoxication. In this study, acetylalanine, a metabolite of acetaminophen, was used as a biochemical indicator for the presence of acetaminophen and was determined in the plasma of mice during and after an acute intraperitoneal application of different doses of acetaminophen in animals which either had access to food or were food deprived. In all experiments food was withdrawn for the 3 hours preceding the treatment with acetaminophen. In the animals receiving free access to food, the plasma levels of acetylalanine were linearly increased during the 4-hour period of acetaminophen application. In animals without food, acetylalanine levels remained almost constant. The higher doses of acetaminophen caused an increased plasma concentration of acetylalanine. However, a dose-related increase in mortality was only found in the animals which had a free access to food. These data demonstrate that the absorption and the toxic effect of acetaminophen depends on the dose of acetaminophen and the time of exposure. Thus, when acetaminophen is ingested within the first 3 hours after food has been removed, only the acetaminophen metabolites can be absorbed, whereas the parent compound is rapidly excreted via the kidneys. From these data the conclusion is that food has a protective effect on acetaminophen toxicity. It is shown that acetaminophen-induced mortality is markedly increased when acetaminophen is ingested after food deprivation. Therefore, this circumstance should be taken into consideration when acetaminophen is applied at home. The mechanism by which food reduces the toxicity of acetaminophen is not known. One possibility is that by this mechanism acetaminophen is completely metabolized by the first-pass effect before it can damage the kidney.