Recently, linkage between the ADA gene locus and MODY, a subtype of NIDDM, has been reported. The possibility that the region of chromosome 20q containing the ADA locus also may play a role in susceptibility to NIDDM needs to be investigated. Therefore, we examined the linkage between the ADA locus and NIDDM in affected siblings of 50 European white diabetic pedigrees--21 Italian and 29 British. Departure from independent segregation of the disease and an Alu VpA polymorphism within the 5' flanking region of the ADA locus was tested in the affected sib-pairs with the APM statistical method. After DNA amplification by the PCR and PAGE, five alleles were identified in the ALU VpA tract at the ADA locus in the two populations. Allele frequencies did not differ significantly between the two populations (chi 2 = 2.426, P > 0.05 [NS]). Analysis of the 50 diabetic sib sets, and independently of the Italian and British groups of affected sib pairs, revealed no segregation distortion between the marker locus and NIDDM. We conclude that mutations within or around the ADA locus are unlikely to play a major role in the etiology of NIDDM.