The present study investigates the effects of acute and repeated nicotine i.p. treatment on cortical EEG activity. Nicotine at 0.3 and 0.9 mg/kg, but not at 0.1 mg/kg, decreased high voltage spindles (HVSs). Nicotine at 2.7 mg/kg suppressed HVSs completely. Mecamylamine, a nicotinic cholinergic antagonist, increased HVSs at 5 and 7.5 mg/kg. Nicotine blocked the HVS induction induced by mecamylamine. Mecamylamine at 1.25 mg/kg antagonized the HVS suppressing action of nicotine at 0.3 mg/kg. The muscarinic cholinergic antagonist, scopolamine (0.2 mg/kg), increased the 1 to 20 Hz amplitude sum value, and this increase was blocked to some extent by the highest dose of nicotine (2.7 mg/kg). However, nicotine did not block the effect of a higher scopolamine (2.0 mg/kg) dose on the sum amplitude values. Mecamylamine at 2.5 and 7.5 mg/kg blocked the effect of nicotine at 2.7 mg/kg on the EEG sum amplitude values in scopolamine (0.2 mg/kg)-treated rats. The peripherally acting nicotinic and muscarinic cholinergic antagonists, hexamethonium and scopolamine methylbromide, had no effect on spectral EEG and HVS values. In quisqualic acid nucleus basalis-lesioned rats, a frontal cortical choline acetyltransferase depletion (-72%) and slowing of the EEG was observed. Nicotine could not restore EEG activity in nucleus basalis-lesioned rats. After repeated (10 days, three injections/day) administration of nicotine, no tolerance to the effects of either nicotine (0.9 mg/kg) on spontaneously occurring HVSs or nicotine (2.7 mg/kg) on the EEG change induced by scopolamine was observed. The present results show that nicotinic receptor stimulation desynchronizes neocortical EEG activity in normal animals, but this action disappears in basal forebrain-lesioned animals. Therefore, it is likely that the effects of nicotine in reversing EEG and behavioral abnormalities observed in Alzheimer's disease may be limited if the basal forebrain cell loss is extensive.