The behavioral effects of lesions of the nucleus basalis magnocellularis (NBM) on two spatial discrimination tasks (place navigation and cross maze) were examined in the rat. These tasks were designed to test reference memory. Lesions by bilateral injection of ibotenic acid into the NBM led to a severe and permanent impairment in the learning of the cross maze task. In the learning of the place navigation task, the rats with lesions showed only a transient deficit. Immediately after the removal of the platform, the rats with lesions explored the quadrant (NE) previously containing the platform as long as controls and above chance levels. The rats with lesions did not extinguish exploration like the controls, seen as a reduction both in time spent in the NE quadrant and in swimming activity. Taken together, the results showed that (1) NBM lesions impair reference memory, but (2) spare other aspects of memory. On the basis of the results in the place navigation task, procedural memory was assumed to remain intact after lesion of the NBM. Biochemical assays of choline acetyltransferase (ChAT) in various brain regions in the lesioned animals demonstrated a reduced ChAT activity in the neocortical projections of the NBM but not in the hippocampus. However, it cannot be decided from this work whether behavioral deficits result from the lesion of cholinergic or of non-cholinergic cells in the NBM.