The brain AT(4) and cholinergic systems play a pivotal role in learning and memory. Studies have investigated the nootropic and amnesic properties of both systems. The cholinergic system has received the most attention for its contribution to cognitive functioning. For example, one of the best known cognitive disorders, Alzheimer's disease (AD), is treated with cholinergic-directed drugs, and post-mortem studies of AD patient brains show neurodegenerative devastation in cholinergic areas of the brain. Studies suggest that potentiation of cholinergic transmission may be a mechanism by which the AngIV/AT(4) receptor system enhances cognition. Since the Nucleus Basalis Magnocellularis (Meynert in humans and primates) (NBM) is a main source of cholinergic innervation to cognitive areas of the brain, this site was chosen to investigate the role and interaction of the two systems. Rats were fitted with permanent bilateral cannulas targeting the NBM for drug administration. Divalinal-AngIV, an AT(4) receptor antagonist produced profound deficits in performance in the Circular water maze. Nicotine treatment reversed these impairments whereas carbachol did not. Similar to the AT(4) antagonist, scopolamine and mecamylamine prevented acquisition of the water maze. Based on these results, it appears that blocking any one of these systems results in impaired spatial learning, while activating the nicotinic receptor system counteracts the effects of AT(4) receptor blockade. These findings suggest a functional role for both the cholinergic and AT(4) receptor systems in spatial learning, and indicate for the first time a functional role for the AngIV/AT(4) receptor system in the NBM.