The intrahippocampal injection of kainic acid cleared 50% of muscarinic receptors and favored the detection of a further 20% loss in hippocampal presynaptic muscarinic receptors produced by electrolytic lesion of the medial septal nucleus as determined by Scatchard analysis of the saturation isotherms of [3H]dexetimide binding. In accordance, a decrease of about 20% in the in vivo accumulation of [3H]dexetimide in the hippocampus was found in animals lesioned in the medial septal nucleus. This effect occurred at both the dose of 5 micrograms/kg and at the saturating dose of 100 micrograms/kg of [3H]dexetimide. The results suggest that the loss was due to decreased receptor number rather than decreased receptor affinity.