Generalized vitiligo is the most common pigmentation disorder, the result of autoimmune loss of melanocytes from the skin and hair, with a high frequency of other autoimmune diseases in vitiligo patients and their relatives. We previously reported the linkage signals on chromosomes 1, 7, and 17 in Caucasian families with generalized vitiligo and associated autoimmune diseases and identified the risk loci of chromosomes 17 and 1 as NLRP1 (NALP1) and FOXD3, respectively. Here, we describe fine-scale genetic association analyses in two independent series of Caucasian multiplex families, refining localization of the chromosome 7 locus and a locus on chromosome 9. Three susceptibility signals, represented by single-nucleotide polymorphisms (SNPs) rs6960920 in 7p13, rs734930 in 7q11, and rs4744411 in 9q22, were significantly associated with vitiligo and other autoimmune diseases. We also detected significant three-way interaction effects of chromosome 7 SNP rs6960920, chromosome 9 SNP rs4744411, and NLRP1 SNP rs6502867 on both the vitiligo phenotype and an expanded autoimmune disease phenotype, and significant three-way interaction effects of both chromosome 7 SNPs and NLRP1 SNP rs6502867 on the vitiligo phenotype. These support the validity of the chromosomes 7 and 9 linkage/association signals and underscore the utility of gene-gene interaction analysis in characterizing the genetic effects of candidate association signals.