The change of cholinergic transmission of beta-amyloid protein (beta-AP) treated rats was studied by intracerebral microdialysis sampling combined with HPLC analysis. beta-AP(1-40) was injected into nucleus basalis magnocellularis (NBM). Passive avoidance response test (step-down test) and delayed alternation task were used for memory testing. The impairment of memory after injection of beta-AP(1-40) into NBM exhibited mainly the deficiency of short-term working memory. One week after injection of beta-AP(1-40) the release of acetylcholine (ACh) from frontal cortex of freely-moving rats decreased significantly, and the response of cholinergic nerve ending to the action of high [K(+)] solution was rather weak. In control animals the percentage of increase of ACh-release during behavioral performance was 57%, while in beta-AP(1-40)-treated rats it was 34%. The temporary increase of the ACh-release of the rat put into a new place was also significantly diminished in beta-AP(1-40) -treated rats. The results show that the injection of beta-AP(1-40) into NBM impairs the cholinergic transmission in frontal cortex, and the impairment of cholinergic transmission may be the main cause of the deficit of working memory.