The prognostic significance of class III major histocompatibility complex complement components, factor B (Bf), C4A and C4B, were studied in a 3-year prospective study of 73 patients with early RA. Patients with C4B null allele had higher disease activity with more radiological progression than patients with C4A null allele or patients without null allele. C4B null allele also associated with increased susceptibility to side effects from antirheumatic treatment. The Bf phenotypes did not associate with the severity of RA. C4B null allele may have prognostic significance in determining a special subgroup of RA patients with a more complicated course of the disease.