RA is associated with a group of class II DR beta alleles, which share a conserved sequence in the third allelic hypervariable region (3AHVR). These include the DR4 subtypes Dw4, Dw14 and Dw15, and also DR1. In contrast Dw10 and Dw13 which are also DR4 subtypes show no association with RA and have a quite distinct 3AHVR. We have assessed the frequency of these alleles in 55 patients who initially presented with symmetrical peripheral polyarthritis suggestive of RA. After 4 years 27 had progressed to definite or classical RA, while 28 had never fulfilled the criteria for this disease. Dw4 was markedly elevated in the rheumatoid group (17/23) compared with either the non-rheumatoids (5/28) or healthy controls (12/100). Dw14 and non-DR4 associated DR1 were not elevated in either group of patients. This study suggests that the DR beta association with RA is likely to facilitate persistence or severity of disease rather than the initial induction of symmetrical peripheral arthritis.