Recent studies have demonstrated that intrahippocampal cholinergic septal grafts can ameliorate deficits in spatial memory function and hippocampal cholinergic neurochemical activity in animals with disruptions of the septohippocampal system. However, no study has determined if the restoration of spatial memory function is correlated to the restoration of cholinergic activity, as measured by high-affinity choline uptake (HACU). The present study was designed to determine if such a correlation between behavioral and neurochemical restoration exists. Male Sprague-Dawley rats received either sham lesions (SHAM), bilateral lesions of the septohippocampal pathway (LES), or bilateral lesions along with intrahippocampal septal grafts (SG). After 8 months, rats were tested for their ability to perform spatial reference, spatial navigation and working memory tasks. Upon completion of the behavioral testing, neurochemical activity of the hippocampus was measured by HACU. The results indicate that animals in the SG group had significantly higher behavioral scores and hippocampal HACU rates than animals in the LES group. Regression analysis indicates that a significant correlation exists between performance on each behavioral task and HACU rates. These results demonstrate that hippocampal cholinergic activity, as measured by HACU, correlates significantly with performance on tests of spatial memory function.