The regional distribution of lithium (Li) and changes in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were examined after dogs had been maintained under conditions of chronic Li intoxication for prolonged periods. The distributions of Li were uneven in the brain. The amygdala, thalamus and hippocampus showed the highest levels, the inner capsule, diencephalon, midbrain, cerebral gray matter, cerebral white matter, medulla and pons contained intermediate levels, while the lowest levels were detected in the cerebellum and spinal cord. There were considerable variations in these levels among the individual dogs. 5-HT levels were decreased significantly in the medulla (to 55% of the control), cerebral gray matter (to 63%) and cerebral white matter (to 75%), and 5-HIAA levels were also decreased significantly in the pons (to 17%), lenticular nucleus (to 42%), cerebellum (to 42%) and inner capsule (to 68%). Correlations between the Li ion levels and the extent of the regional 5-HT or 5-HIAA decrease were nil. The extent of the decrease in the levels of these compounds seems to be dependent not on the Li levels but rather on the vulnerability of each brain region.