Thirty-three Israeli patients with systemic lupus erythematosus (SLE) were studied for their ability to respond to the synthetic polypeptide poly (Tyr,Glu)-poly (DLAla)-poly(Lys) [( T,G]-A-L) as measured by the production of a T cell helper factor by their antigen activated T cells. Twenty-seven of the patients were typed for their HLA phenotypes. Nineteen patients were with more active disease and 14 with a milder non-active disease. All the patients of the two groups responded to (T,G)-A-L by the production of an antigen specific helper T cell factor, in contrast to only 50% responders among healthy donors. Thus, lack of normal regulation of T cell helper function was observed among all patients with SLE, independently of their disease activity and/or treatment. A higher frequency of DR5 (75%) was observed in patients with a milder non-active disease (vs 46.6% in normal healthy control individuals) while 53.3% of patients with active disease possessed DR7 (21.8% in controls). These findings may suggest a possible association between the severity of the disease and a specific DR determinant.