Fifty-two British and 29 Greek idiopathic membranous nephropathy (IMN) patients were analysed for DRB, DQA1, DQB1 and DPB1 gene polymorphism using second exon amplification and sequence-specific oligonucleotides (SSO). In addition 100 British and 92 Greek controls were analysed. A highly significant increased frequency of the DRB1*0301 allele was found in IMN patients from Britain (80%), when compared to controls (27%, OR 10.6, P = 0.000004). A lower frequency of DRB1*0301 was observed in Greek IMN patients (33%), but this was just significant before correction, when compared to Greek controls (15%, OR 3, P = 0.02). The DRB3 allele most often associated with DRB1*0301 was DRB3*0101 (OR 4.2, P = 0.00025) in British patients and DRB3*0201/2 (OR 11, P = 0.006) in Greek patients. In Greek IMN patients a decrease in DR16 was found (OR 0.08, P = 0.004), and the overall incidence of DR2 was significantly lowered when both sets of IMN patients were combined (OR 0.21, chi 2 17.6, P = 0.00013). The incidence of DQA1*0501 was raised in both Greek (96% vs. 66%, OR 9.7, chi 2 6.9, P = 0.009) and British IMN (85% vs. 45%, OR 7.4, chi 2 20, P = 0.00007) patients. This gives some support to a proposal for a major role for this allele in IMN.(ABSTRACT TRUNCATED AT 250 WORDS)