Using the quantitative trait loci (QTL) approach, preliminary identification has been made of a region on mouse chromosome 17 that influences high-affinity choline uptake (HACU) in the mouse brain. The rate of HACU was measured in synaptosomes prepared from the frontal cortex, hippocampus, and striatum of C57BL/6J (B6), DBA/2J (D2), and 25 BXD recombinant inbred (RI) strains of mice, using a final concentration of 0.5 microM [3H]choline. The strain means of HACU in each area were then correlated with the strain distribution pattern of each of 1300 known genetic markers using a point biserial correlation and 0 (B6 allele) and 1 (D2 allele). Correlations of P < 0.00001 were found between striatal HACU and chromosome 17 markers D17Tu50 and Tcp1. Correlations of P < 0.0001 were found between striatal HACU and chromosome 17 markers D17Leh66e, D17Leh119, D17Rp17e, Plg, D17Leh66d, Ckb-rs2, and Trp53-ps. QTL analyses of HACU in the frontal cortex and hippocampus also revealed correlations with these markers at the level of P < 0.05 and P < 0.01. These data suggest that at least one locus located on mouse chromosome 17 near or between 6 and 13 cM from the centromere influences HACU in the striatum and possibly the frontal cortex and hippocampus of the mouse.