Haplotype blocks characterized from 78 single-nucleotide polymorphisms (SNPs) in a 1- to 2-centiMorgan region in the human diabetes susceptibility gene IDDM17 were tested for association with type 1 diabetes mellitus (T1DM). Two haplotypes in two adjacent blocks in AMACO, a von Willebrand factor homologue, appear to be associated with the absence of T1DM; transmission tests support this hypothesis. Interestingly, in both haplotype blocks, a single SNP distinguishes the protective haplotype from the other haplotypes. One SNP is noncoding, whereas the other SNP causes a change from glutamic acid to glycine. Future work in identifying the protective allele includes association tests of block haplotypes in other populations.