Adult male Long-Evans rats were subjected to bilateral lesions of the cholinergic neurons in the nucleus basalis magnocellularis (NBM) by injection of 0.2 or 0.4 mug 192-IgG-saporin in 0.4 mul phosphate-buffered saline, Control rats received an equivalent amount of phosphate-buffered saline. Starting 2 weeks after surgery, all rats were tested for locomotor activity in their home cage, beam-walking performance, T-maze alternation rates (working memory), reference and working memory performance in a water-maze task, and memory capabilities in the eight-arm radial maze task using uninterrupted and interrupted (delay of 2 min, 2 h and 6 h after four arms had been visited) testing procedures. Histochemical analysis showed a significant decrease of acetyleholinesterase (AChE)-positive reaction products (30-66%) in various cortical regions at the 0.2-mug dose. At the dose of 0.4 mug, there was an additional, although weak, damage to the hippocampus (17-30%) and the cingulate cortex (34%). The behavioral results showed only minor impairments in spatial memory tasks, and only during initial phases of the tests (reference memory in the water maze, working memory in the radial maze). The behavioral effects of the dramatic cholinergic lesions do not support the idea of a substantial implication of cholinergic projections from the NBM to the cortex in the memory processes assessed in this study, but they remain congruent with an involvement of these projections in attentional functions. (C) 2002 Elsevier Science Inc. All rights reserved.