Unilateral lesions with ibotenic acid in the vicinity of the mammillary bodies where the histamine (HA)-secreting neurons are located induced bilateral reductions in the levels of HA in the posterior hypothalamus (40-60%), anterior hypothalamus (45%), and frontal cortex (30%) as well as in the ipsilateral hippocampus (40%) 7 days after injection. Changes in the concentration of HA in the median eminence and adenohypophysis were not significant, but in the neurohypophysis the content of HA increased by 80%. These results seem to indicate that intrahypothalamic and cortical HA pathways are bilateral in origin while hippocampal HA pathways are predominantly ipsilateral.