The levels of histamine in the cerebral cortex, cerebellum, midbrain and caudate nucleus of adult male rats were determined fluorometrically every 3 h over a 24 h period in control animals and in animals injected, 30 min earlier, with 50 mg/kg phenobarbital, 40 mg/kg pentylenetetrazol or 8 mg/kg picrotoxin. All the animals were adapted for at least three weeks to an LD 12: 12 illumination regime. Results show that histamine levels in the brain areas studied, particularly in the caudate nucleus, were highest during the dark phase and lowest during the light phase of the cycle. Phenobarbital, pentylenetetrazol and picrotoxin consistently decreased histamine levels during the dark phase while increasing the levels of histamine during the light phase of the cycle in these brain areas, thus phaseshifting the rhythmic pattern of the amine, particularly in the cerebral cortex and caudate nucleus in the cases of phenobarbital and picrotoxin and in the caudate nucleus in the case of pentylenetetrazol.