Fifty-five Danish families with two offspring concordant for type 1 diabetes-identified through a nationwide population-based survey, and 57“true sporadic”cases-matched with familial cases for age at onset, but with no IDDM-affected first-degree relatives and long disease duration, and 110 control subjects were typed for putative genetic susceptibility markers for type 1 diabetes identified from a pathogenetic model. The markers included MHC class I, II and III loci, the manganese superoxide dismutase (MnSOD) locus (chr. 6q), interleukin-1β(IL1B), the IL-1 receptor antagonist (IL1RN), and the IL-1 type 1 receptor (IL1RI) loci (each chr. 2q). No significant differences between familial and sporadic cases were found within the MHC region (including the following loci: HLA-DQ,-DR, heat shock protein (HSP) 70, tumour necrosis factor (TNF), HLA-B and-A). In both groups of patients 11% were negative for both DQA1*0301-DQB 1*0302 and DQA1*0501-DQB1*0201 genotypes, and 7% of the type 1 diabetics had genotypes unable to encode a susceptibility DQαβheterodimer. Disease association was found for the IL1RN (p= 0.04) and for the IL1RI (p= 0.03). When comparing controls and only familial cases with type 1 diabetes for the IL1RN polymorphism a difference was observed (p= 0.003). For the IL1B RFLP a trend for difference was observed between familial cases and control subjects (p= 0.046), whereas no differences between sporadic cases and control subjects could be demonstrated neither at the IL1B nor at the IL1RN loci. A difference in the MnSOD pattern was observed between sporadic cases and controls (p= 0.04).