Ethanol and nicotine have many psychopharmacological effects in common, which could explain why coadministration of these compounds often is observed in individuals. In the present study in mice, low doses of nicotine in a complex manner altered the locomotor activity (LMA) stimulatory effect of different doses of ethanol, whereas the quaternary nicotine analog tetramethylammonium did not. The blood-brain-barrier-penetrating nicotine antagonist mecamylamine (2.0 and 4.0 mg/kg), but not the quaternary nicotine antagonist hexamethonium (4.0 and 8.0 mg/kg), partly counteracted the LMA stimulatory effect of ethanol (3.0 g/kg) in doses having no LMA reducing effects per se. Furthermore, the dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) quotient increase in mouse brain after ethanol 3.0 g/kg was partly antagonized by mecamylamine 2.0 and 4.0 mg/kg. These results suggest that part of the LMA and DA turnover-increasing effect of ethanol is mediated via activation of central nicotinic acetylcholine receptors.