The age-related changes and the acute effects of intravenous melatonin on the activity of striatal neurons of 1-, 3-, 6-, 12-, and 18-month-old sham-operated and pinealectomized rats were investigated. There was a decline in responsiveness from 3- to 18-months of age, although in sham-pinealectomized rats the responses were similar at 12 and 18 months; in pinealectomized rats, the neuronal responses were quite stable at early ages. In all age groups of sham-pinealectomized rats, neuronal firing decreased in most cells, and increased in only a small percentage of cells after intravenous melatonin injection (100 ng/kg). However, in pinealectomized rats, the injection of melatonin at the same doses significantly increased the firing rate of most neurons compared to that in sham-operated animals at all age-groups, while the number of neurons showing an inhibitory response decreased. These results indicate that melatonin may be involved in the modulation of the activity of striatal neurons and demonstrates an age-dependent reduction in striatal sensitivity to melatonin. They also suggest that other compounds of pineal origin may modulate the activity of motor control centers.