To identify new loci predisposing to insulin-dependent diabetes mellitus (IDDM), we have investigated 250 families with more than one diabetic child. Affected sibling pair linkage analysis revealed strong evidence for an IDDM susceptibility locus near D15S107 on chromosome 15q26 (P = 0.0010) termed IDDM3. Families less predisposed through genes in the HLA region provided most of the evidence for linkage. In these families, discordant sibling pairs also showed linkage (P = 0.0052), and sibling pair disease concordance or discordance was strongly related to the proportion of genes the pair shared at D15S107 (P = 0.0003). Our study also revealed evidence for an IDDM locus on chromosome 11q13 (IDDM4) using affected siblings (P = 0.0043), but no evidence using discordant siblings.