A poor prognosis was observed in patients who had end-stage renal disease (ESRD) as a result of systemic lupus erythematosus (SLE). This was true even in patients in whom SLE disease activity was transiently quiescent during the period of hemodialysis. Six of 9 patients with ESRD and SLE died with active SLE and/or sepsis 1-28 months following the onset of dialysis. In 5 of the 6 patients, acute inflammatory activity of SLE flared within 1 month of the patient's death. Four patients died with superimposed sepsis, but only 2 of the 4 were receiving high-dose concomitant immunosuppressives for more than 1 week prior to death. Infected hemodialysis vascular access sites were implicated as the source of septicemia in 3 of 4 infectious deaths. The 3 surviving patients had minimal lupus activity prior to the development of ESRD, a possible marker for stability in SLE patients who require hemodialysis. Our results suggest that hemodialyzed lupus patients with nonautologous vascular access sites may be at continued increased risk for life-threatening inflammatory and septic complications.