DNA from 164 Caucasian type I (insulin-dependent) diabetic patients and 200 Caucasian nondiabetic control blood donors were analyzed by the polymerase chain reaction technique for HLA-DR4 and the associated Dw and DQB subtypes of DR4. The DQw8 subtype of HLA-DR4 was associated with type I diabetes in all DR4 subgroups (DR4/3 and DR4/non-3). Dw subtypes of DR4 other than DW10 did not confer additional association with type I diabetes. Thus, the DQ region appears to provide the primary major histocompatibility association with type I diabetes in most DR4 patients.