The effects of increasing doses of ethanol on locomotor activity and on the metabolism of dopamine (DA) in the limbic forebrain and in the striatum of CBA, C57Bl, and NMRI mice were studied. In NMRI mice, low doses of ethanol produced locomotor stimulation which was followed by inhibition of locomotor activity at higher doses. In C57Bl and CBA animals, ethanol caused only reduction of locomotor activity. A low dose of ethanol (2.25 g/kg, i.p.) produced a significant enhancement in the release of DA (measured as the ratio DOPAC/DA) in limbic brain structures of all animals with no corresponding effect in the striatum. A high dose of ethanol (4.5 g/kg, i.p.) significantly increased the DOPAC/DA ratio both in the limbic forebrain and in the striatum of all animals. The significance of these behavioral and biochemical observations with regard to genetic aspects on the role of DA in the stimulatory/reinforcing properties of ethanol and to previously observed genetic differences in other neurotransmitter systems, especially GABA and glutamate, is discussed.