Abstract Background Although many years of genetic epidemiological studies have demonstrated that genetics plays a significant role in determining smoking behavior, little information is available on genomic loci or genes affecting nicotine dependence. Several susceptibility chromosomal regions for nicotine dependence have been reported, but few have received independent confirmation. To identify susceptibility loci for nicotine dependence, 313 extended pedigrees selected from the Framingham Heart Study population were analyzed by both the GENEHUNTER and S.A.G.E. programs. Results After performing linkage analyses on the 313 extended Framingham Heart Study families, the EM Haseman-Elston method implemented in GENEHUNTER provided evidence for significant linkage of smoking rate to chromosome 11 and suggestive linkage to chromosomes 9, 14, and 17. Multipoint sib-pair regression analysis using the SIBPAL program of S.A.G.E. on 1389 sib pairs that were split from the 313 extended families identified suggestive linkage of smoking rate to chromosomes 4, 7, and 17. Of these identified positive regions for nicotine dependence, loci on chromosomes 7, 11, and 17 were identified by both GENEHUNTER and S.A.G.E. programs. Conclusion Our genome-wide scan results on the Framingham Heart Study data provide evidence for significant linkage of smoking rate to chromosome 11 and suggestive linkage to chromosomes 4, 7, 9, 14, and 17. These findings suggest that some of these regions may harbor susceptibility loci for nicotine dependence, and warrant further investigation in this and other populations.