In the present study we analysed the neuroprotective effect of the L-type voltage-dependent calcium channel antagonist verapamil on cholineacetyltransferase (ChAT)-immunoreactive neurons in the cerebral cortex of rats with bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM). Treatment with verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg/12 h i.p.) started 24 h after NBM lesions and lasted 8 days. Animals were sacrificed on day 21 after NBM-lesions. The bilateral NBM-lesions produced significant loss of ChAT-immunoreactive neurons in frontal, parietal and temporal cortex. Although the number of ChAT-positive neurons was significantly higher in NBM-lesioned animals treated with verapamil at a dose of 2.5, 5.0 and 10.0 mg/kg than in saline treated ones, the most significant effect was obtained at a dose of 5 mg/kg. This is, to our knowledge, the first report showing an inverted U-shape mode of neuroprotective action of the calcium antagonist verapamil, at morphological level in this particular model of brain damage. The demonstrated beneficial effect of verapamil treatment suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a possible treatment to prevent neurodegenerative processes in the rat cerebral cortex. © Springer-Verlag 2005.