Doses of 6-hydroxydopamine (6-OHDA) from 1 to 6 microgram injected into the right frontal cortex of rats led to spontaneous hyperactivity beginning 1 week after injection and lasting throughout the 30-day postoperative period. Identical left hemispheric injections did not elicit hyperactivity until a dose of 6 microgram was reached. Biochemical assays revealed that 6-OHDA injected into either hemisphere caused approximately the same amount of depletion of norepinephrine. These results suggest that the neural asymmetry which leads to hyperactivity may be post-synaptic to the cortical noradrenergic terminals.