Type 1 diabetes mellitus (IDDM) is an autoimmune disorder in which the alleles HLA DQA1*0501-DQB1*0201 and DQA1*0301-DQB1*0302 confer strong susceptibility. The genes for transporters associated with antigen processing (TAP1 and TAP2) are located near HLA DQ and display only a limited degree of polymorphism. Since polymorphisms of TAP might influence susceptibility to IDDM possibly by selection of different antigen peptides, we investigated sequence variants of TAP1 and TAP2 genes in 120 German patients with IDDM and 218 random healthy German controls by polymerase chain reaction (PCR) followed by sequence-specific oligonucleotide analysis (SSO), single-strand conformation polymorphism (SSCP) analysis and amplification refractory mutation system (ARMS). TAP1*02011 (16% vs. 4% in controls, P = 0.001, RR = 5.0) and TAP2*0101 (96% vs. 69% in controls, P < 0.0001, RR = 10.6) showed a positive association with IDDM. However, these associations disappeared when patients and controls were matched for predisposing HLA DQA1 or DQB1 alleles as well as for DRB1*0401. In conclusion, our findings indicate that the observed association of TAP variants with IDDM in German patients is due to linkage disequilibrium with HLA DQ alleles/DRB1*04 subtypes.