A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1 (497-513) AVTPL RIFIVPPAAEY has an 11 amino acid identity with HLA-DQw8 beta (49-60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496-515) peptide crossreacted with the homologous DQw8 beta (44-63) peptide but not with the related DQw7 beta (44-63) peptide, which differed from the DQw8 peptide only in an ALA to ASP substitution in position 57. Antisera to DQw8 beta (49-60) reacted with the DQw8 beta (44-63) peptide and BOLF1 (496-515), but not with DQw7 beta (44-63). The antiserum to the BOLF1 peptide bound to denatured class II major histocompatibility complex beta chains from Epstein-Barr virus-transformed DQw8-positive lymphocytes in an immunoblotting analysis. Epstein-Barr virus antibodies were detected at equal frequencies and similar titres in sera of 30 patients with Type 1 diabetes (16 of 30; 63%) and in sera of 20 non-diabetic control subjects (13 of 20; 65%). Sera from diabetic patients did not bind to DQw8 beta (44-63) or BOLF1 (496-515) peptides. From these data we conclude that there is no simple relationship between serological evidence of Epstein-Barr virus infection and crossreactions between homologous Epstein-Barr virus and class II major histocompatibility complex peptides.