Brain edema is a leading cause of death in acute liver failure (ALF). In experimental models of ALF, an increase in the content of brain water has been inferred indirectly by measuring intracranial pressure or determined directly via analysis of brain tissue postmortem. In this study, noninvasive proton two-dimensional chemical shift imaging (2-D CSI) was used to follow the time course of the development of brain edema in a well characterized model, namely ammonium acetate infusion into rats 48 to 72 h after portacaval anastomosis (PCA). Clear differences between control and experimental rat brains were observed, with an increase of brain water signal only in the parietal cortex of the PCA + ammonia group. Selective swelling of the cerebral cortex points to a cytotoxic mechanism in the evolution of brain edema in this model. CSI signal enhancement was much greater than the gravimetrically determined water content increase. The significantly greater signal change observed with 2-D CSI may reflect enhanced proton density that results from increased water content as well as edema-related alterations in water relaxation times.