Abstract We present evidence that in MRL/Mp mice, difference in one gene affects the activity of alcohol dehydrogenase. MRL/Mp- + show high alcohol dehydrogenase (ADH) activity in the range of that found in C57BL/6, while MRL/Mp-1pr show ADH values in the range of non-drinker strains such as DBA/1, BALB/c, A, SJL, CBA and C3H/He. Voluntary alcohol consumption in MRL/Mp- + is 30–40% higher than that in the MRL/Mp-1pr. However, alcohol preference of both congenic strains is markedly lower than those of C57BL/6 mice. Our findings lead us to conclude that although alcohol dehydrogenase levels do relate to alcohol preference in mice, they are responsible for only a minor fraction of inter-strain differences.