Neurologic and radiologic disorders have been reported to occur in miners inhaling manganese (Mn)-laden dust and in humans receiving long-term parenteral nutrition. These abnormalities have been attributed to Mn intoxication because of elevated serum Mn concentrations. Because the liver, by way of the bile, is the major route of Mn excretion, it is possible that anything that decreases biliary excretion could increase accumulation of Mn in the brain. The purpose of this study was to determine whether biliary ligation would increase Mn accumulation in the brain of rats that were exposed to deficient or adequate amounts of dietary manganese. The first experiment had a 2 x 3 factorial design, two levels of Mn (0 or 45 microg/g diet) and three surgical treatments (control, sham, or bile-ligation). Animals were sacrificed 10 d after being fed 54Mn. In experiment 2, animals that had a sham operation or bile-ligation were sacrificed at 8 time points after being injected intraportally with 54Mn complexed to albumin. The biliary-ligated animals had a significantly (p < 0.001) smaller percentage of the 54Mn in their brains (when expressed as a percentage of whole animal 54Mn) than the sham-operated animals. Mn deficiency had a similar effect. However, we did observe an increased accumulation of the radioisotope in the brain over time. Therefore, in short-term studies, biliary-ligated rats do not appear to be a good model for Mn accumulation in the brains of people with cholestatic liver disease.