Despite some evidence that smoking behavior is influenced by both genetic and environmental factors, efforts at identifying specific genes that influence smoking are extremely limited. Using information on smoking behavior history for 973 individuals distributed across 105 COGA families and a multipoint variance components method, we tested for linkage between smoking behavior (as defined by number of cigarette packs per day for 1 year) and chromosomal locations across the genome using information from 296 markers. We found strong evidence (lod = 3.2) for linkage of smoking behavior to a genetic location on chromosome 5q (D5S1354). Weaker evidence was found for linkage of smoking behavior to genetic locations on chromosomes 4 (between markers D4S244 and D4S2393), 15 (D15S642), and 17 (GATA193). Oligogenic linkage analyses suggest the putative locus on chromosome 5q is the primary determinant of genetic variation in smoking. Although the magnitude of the lod score is compelling, the large gap between the markers D5S1456 and D5S1354 (which is also at the end of chromosome 5q) in the COGA data set reduces the enthusiasm for this putative quantitative trait locus. However, typing of additional markers in this region may provide greater support for the localization of a susceptibility locus at this chromosomal location, which is not far from the DRD1 (D1 dopamine receptor gene) locus.