The effects of separate and concurrent lesions to the cholinergic and noradrenergic (NE) systems were assessed in two water mazes. Lesion of the nucleus basalis magnocellularis (NBM) decreased performance in a spatial memory task (Morris water maze) while lesions of the dorsal NE bundle (DNB) enhanced the acquisition of this task independent of the NBM effects. Both lesions impaired performance on a water-escape motivated T-maze; however, the deficits induced by the combined lesion did not differ from the effects of either lesion alone. Neither lesion, nor their combination, had significant effects on open field activity. Biochemical analyses revealed almost total loss of NE in the cortex and hippocampus after DNB lesion, with relatively minor changes in other catecholamines or metabolites. Choline acetyltransferase activity was not significantly altered by the DNB lesion but was decreased in the cortex by the NBM lesion. These results suggest a task-specific effect of DNB lesion that is detectable under conditions of mild stress when floor effects are minimized.