The purpose of our study was to examine evidence for the role of a second genetic factor in the susceptibility to IDDM, in addition to that located in the HLA region. To do this, we have studied the joint segregation of HLA and another marker conditional on disease status using the IDDM families of GAW5, under a two-locus model, one locus in the HLA region, the other close to the other marker. This marker has been, successively, Gm and the DNA polymorphism of the insulin gene 5′ region. The study has been carried out using a segregation analysis method developed to make use of information on the segregation of two markers and the disease in nuclear families. The GAW5 data do not provide evidence for the role of a genetic factor in the Gm or insulin region in the etiology of IDDM.