These experiments tested the role of cholinergic mechanisms in the changes of cerebral cortical blood flow (CBF) induced by brain trauma. CBF was measured with Iodo-14C-antipyrine autoradiography, in 128 cerebral cortex regions of both hemispheres, distributed in eight coronal slices. The effects of a 6.3-mm diameter craniotomy over the left motor-sensory cortex with no weight drop, and of trauma (drop weight of 20 g from 30 cm height on left motor-sensory cortex through a 6.3 mm circular craniotomy) on CBF were studied at 2 and 24 h after the interventions. A group of control animals that received no intervention was also set up. Animals were treated with the cholinesterase inhibitor physostigmine salicylate (3.3 microg/kg/min i.v. infusion started 60 min before CBF measurements), the cholinergic blocker scopolamine hydrobromide (1 mg/kg i.v. pulse, 18 min before CBF measurements), or with the drugs vehicle (saline). A focus of decreased CBF at the site of impact was observed 2 h after trauma, extending caudally as far as the occipital cortex. CBF on the contralateral cerebral cortex was also decreased. Both phenomena reversed partially at 24 h. This spontaneous recovery of CBF was blocked by scopolamine. Physostigmine reversed the decrease in CBF of the traumatized cortex, partially around the contused area and completely in more distant regions. The cerebral cortex contralateral to the trauma showed significantly higher CBF 24 h after trauma when compared to intact controls or craniotomy that peaked at the area symmetrical to the center of trauma. This phenomenon was also enhanced by physostigmine and completely blocked by scopolamine. These results suggest a prominent role of cholinergic mechanisms in the vascular adjustments that accompany cerebral trauma.