Differential sensitivity to the stimulant effects of ethanol on locomotor activity is determined in part by genetic differences. Among inbred strains of mice, moderate doses of ethanol (1-2 g/kg) stimulate locomotor activity in some strains, e.g., the DBA/2J (D2), but only mildly affect activity in other strains, e.g., C57BL/6J (B6) (Crabbe et al., 1982, 1983; Crabbe, 1986; Dudek and Phillips, 1990; Dudek et al., 1991; Dudek and Tritto, 1994). Quantitative trait loci (QTL) for the acute ethanol (1.5 g/kg) locomotor response has been identified in the BXD recombinant inbred (RI) series (N = 25 strains), a C57BL/6J x DBA/2J (B6D2) F2 intercross (N = 1800), and heterogeneous stock (HS) mice (N = 550). QTLs detected (p < .01) in the RI series were found on chromosomes 1, 2, and 6 and these QTLs were expressed in a time-dependent fashion. The QTLs on chromosomes 1 and 2 were confirmed in the F2 intercross at p < 10(-7) or better. HS mice from G32 to G35 were used to fine-map the chromosome 2 QTL. Compared to the consensus map, the genetic map in the HS animals was expanded 10- to 15-fold. Over the region flanked by D2Mit94 to D2Mit304, three separate QTLs were detected in the HS animals. The data obtained confirm the usefulness of HS mice for the fine-mapping of QTLs to a resolution of 2 cM or less.