The aim of this study was to investigate the modulation of the hippocampal function by the cholinergic cells of the septum and the role of the septo-hippocampal cholinergic system in learning and memory. Immunotoxin 192 IgG-saporin was used to produce selective lesions of cholinergic septohippocampal neurons. Hippocampal AChE was used as a quantitative measure of lesion extent. A total of 16 male outbred albino rats were used in the present study to investigate the ability of sham-operated and medial septal (MS) immunotoxin lesioned rats to learn the location of a visible, as well as submerged platform in a water maze. The rats' responses on the competition test were classified as either cue or place, based on the swim path for those trials. Examination of the AChE stained sections showed that after injections of 192 IgG saporin into the MS, animals exhibited significantly less AChE staining in hippocampus as compared to sections obtained from sham-operated animals. Differences in the platform reaching latency between the animals of different groups for the training trials were not found. Data from both competition trials for each group show that the sham-operated rats in 13 trials out of 16 competition test trial used place strategy and MS-lesioned ones used this strategy in 11 trials. Decreased place-bias in MS-lesioned rats compared to the sham-operated rats was not significant. These findings suggest that the septo-hippocampal cholinergic system is not essential for all types of hippocampal-dependent memory and deficits observed after septal electrolytic lesions cannot be accounted solely to the loss of hippocampal ACh.