In rats, nonspecific mechanical or neurotoxic lesions of the septum impair spatial memory in, e.g., Morris water‐ and radial‐maze tasks. Unfortunately, the lack of specificity of such lesions limits inferences about the role of the cholinergic hippocampal projections in spatial cognition. We therefore tested the effects of septal lesions produced by 192 IgG‐saporin in rats, which is highly selective for basal forebrain cholinergic neurons, on home cage activity, noncognitive tests (modified Irwin test, open field and forced swimming tests, and various sensorimotor tasks), and the cone‐field spatial learning task. The immunotoxic lesion reduced acetylcholine (ACh) levels in the septum (−61%) and hippocampus (>−75%). Rats with lesions showed mild home‐cage hyperactivity at 4 weeks postlesion, but no noncognitive deficits at 13 weeks postsurgery. In the cone‐field task, rats with septal lesions made more working‐ and reference‐memory errors than the controls, but acquisition curves were parallel in both groups. The speed of visiting cones was faster in the rats with lesions, indicative of disturbed attention or increased motivation. These data support the growing evidence that involvement of the septohippocampal cholinergic system in spatial learning and memory may have been overestimated in studies that used lesions with poor selectivity. © 2006 Wiley‐Liss, Inc.