We performed retrospective analysis of 141 Northern Italian patients with rheumatoid arthritis (RA). This series represents all the patients seen as in and/or outpatients at the rheumatologic unit of Reggio Emilia Hospital during a 2 year period (1987-88). We observed a low frequency of nodules (16%) and vasculitis (2.1%). Thus, RA seems to be milder in our population compared to Caucasian patients with RA originating from North America or England. We observed a weak association with DR4 (RR = 2.4) in the total group of patients with RA. A low frequency of DR4 was observed in patients and controls (29 vs 14.5%, p = 0.001). When compared with controls the frequency of DR4 was significantly higher in seropositive (p = 0.001), but not in seronegative patients. We found that DR4 was significantly associated with nodules (RR = 6.4), with extraarticular features (EAF) (RR = 4) and with erosions (RR = 3) compared with controls. The subgroups with nodules and EAF had a DR4 frequency (respectively, of 52 and 40%) which was significantly higher than that observed in remaining patients (respectively, 25 and 24%). No significant difference was observed in the DR4 frequency between the patients with erosions and those without (34 vs 18%). Thus, DR4 in our population seems to be predominantly associated with a subgroup of patients characterized by seropositivity and EAF.