Of 240 adults with sickle cell anemia seen over 11 years, 12 had the nephrotic syndrome. In 9 (75%) the glomerular lesion, sickle glomerulopathy, consisted of mesangial expansion and basement membrane duplication. Six patients had type IV renal tubular acidosis. Four of the 9 Patients died within 24 months (17 +/- 5; mean +/- SD), while 5 survived 36 months or longer (80 +/- 49); no significant differences were seen between the former and the latter in age, admission serum creatinine and C3 levels, urinary protein excretion, or the frequency of renal tubular acidosis. Chronic azotemia developed in 3 and acute renal shutdown in another 2. Of 22 patients with sickle glomerulopathy (our 9 added to 13 from the literature) 11 died within 2 years. Ten of these (91%) had developed renal failure, compared to only 5 of the 11 (45%) who survived longer than 2 years (p less than 0.05). The 5-year mortality in the general population of sickle cell anemia is 3.75%, and 75% of patients aged 15 years or older survive 18 years or longer. The nephrotic syndrome, most often caused by sickle glomerulopathy, occurs in 4% of patients with sickle cell anemia, leading to renal failure in two-thirds and death in 2 years in half the patients. The development of chronic azotemia correlates strongly with early mortality. The prognosis is much worse than that in the general population of sickle cell anemia.