To determine if repeated administration of desipramine (DMI) or electroconvulsive shock (ECS) regulate uptake sites for norepinephrine (NE) in rat brain, the binding of [3H]nisoxetine ([3H]NIS) was measured using quantitative autoradiography. Groups of animals were given DMI intraperitoneally, either a single injection or repeated doses of 10 mg/kg once daily for 21 days and were killed 48 h after the last injection. Another group of rats received ECS daily for 12 days (150 mA, 300 ms, 60 Hz) and was killed 24 h after the last shock. Repeated administration of DMI caused statistically significant decreases (20-40%) in the binding of [3H]NIS in 8 out of 17 brain regions measured; these areas included the hippocampus, thalamus and the amygdala. Acute treatment with DMI had no effect on the binding of [3H]NIS in any of the regions analyzed except the centrolateral nucleus of the amygdala. By contrast, except for the paraventricular nucleus of the thalamus where ECS caused a modest (20%) increase in binding, no other brain region was affected by ECS. Thus it appears that repeated administration of DMI and chronic ECS treatment have different effects on the binding of [3H]NIS to uptake sites for NE in rat brain.