In this study, we investigated the effects of 192 IgG saporin injections into the medial septal area (MSA), or nucleus basalis magnocellularis (NBM), and combined injections into the MSA and NBM, on water maze and radial arm maze performance in the male rat. The results of the present study reveal a dissociation between the effects of 192 IgG saporin injections into the basal forebrain on the performance of two tasks of spatial learning in the rat. Bilateral injections of 192 IgG saporin into the NBM, MSA or combined MSA/NBM failed to disrupt water maze performance when compared to controls. In contrast, injections of 192 IgG saporin into the MSA, NBM or MSA/NBM induced mild impairments on a radial arm maze task. Overall, the disruption of spatial learning observed in this study was, however, relatively mild compared to deficits in spatial learning reported using less selective lesions of the cholinergic basal forebrain. Consequently, the results of this study suggest that a selective reduction in cholinergic transmission in the basal forebrain is, by itself, insufficient to account for the functional impairments observed in spatial learning in the rat. Although our data do support the use of 192 IgG saporin as a selective cholinergic toxin in the basal forebrain, they further suggests that assessment of spatial learning in the rat following 192 IgG saporin lesions of the basal forebrain in combination with lesions to other neurotransmitter systems, may be a more viable approach to the elucidation of the neuropathological mechanisms that are associated with the cognitive deficits seen in Alzheimer's disease.