Identical female twins clinically discordant for 20 years for SLE were studied. Their HLA-haplotype was A1,28; B8w6,w35; Cw3,w7; Dr3,4. Both twins had a raised erythrocyte sedimentation rate, autoantibodies, and circulating immune complexes. The diseases sibling had a reversed OKT4/OKT8 ratio (0.43), decreased helper T cell number, defective pokeweed mitogen (PWM) induced plasma cell differentiation, and overactive hydrocortisone sensitive suppressor cells. Immunological abnormalities may be only partly HLA related (B8; Dr3), but are most probably secondary to the disease process in the sibling with SLE. Exogenous and/or endogenous factor(s) other than genetic or immunological are suggested as being operative in the predisposition to and expression of SLE.