Significant differences in both the affinity and IgG subclass of antibodies produced after immunization with tetanus toxoid have been demonstrated in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls. Patients with RA failed to show affinity maturation although they produced similar amounts of antibody to the controls. Some patients with SLE produced very high affinity antibodies although there was a wide spectrum of response. Antibodies to tetanus toxoid in controls were predominantly IgG1 and IgG4 but in RA and SLE there was either a restricted IgG1 response or a more general response in all the IgG subclasses. It is likely that these differences in response reflect the underlying disorders in immunoregulation present in patients with these diseases.