Studies were made on the effects of blockade of muscarinic acetylcholine (mACh) receptors in the rat cerebral cortex on learning and memory assessed by performance of a step-through passive avoidance task. Bilateral injection of propylbenzilylcholine mustard (PrBCM) into both the frontal and parietal cortex at doses of 2.25 X 4 to 22.5 X 4 micrograms decreased mACh receptors dose-dependently, as assessed by [3H]quinuclidinyl benzilate binding studies. When the training trial of a step-through passive avoidance task was performed 24 h after injection of 7.5 X 4 to 22.5 X 4 micrograms PrBCM into the frontal and parietal cortex, and then a retention test was made 24 h after the training trial, the treated rats showed shorter latencies than controls. In contrast, injection of PrBCM into the occipital cortex had no significant effect on performance in the test. These results confirm the notion that cholinergic neurotransmission in the cerebral cortex, especially the frontoparietal cortex, is important in learning and memory. The effects of injection of PrBCM (22.5 X 4 micrograms) into the frontoparietal cortex on 3 postulated phases of the learning and memory process (i.e. registration, retention and recall) were also examined. When PrBCM was injected 24 h before the training trial, no retention of the task was observed 14 days after the training trial. However, when PrBCM was injected 24 h after the training trial, retention of the task 14 days after the training trial was not affected. When PrBCM was injected 3-24 h after the initial training trial, the latencies in the retention test examined 24 h later were shorter than those of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)