We performed a cross sectional analysis of glomerular function in 34 adult patients with sickle cell anemia (SSA). Patients were divided according to GFR and albumin excretion rate (AER): SSA controls (normal GFR and AER, N = 10), albuminuria (increased AER, but normal GFR, N = 7) and chronic renal failure (CRF, low GFR, N = 17). GFR did not correlate with age (that is, duration of disease), but was inversely related to AER and IgG excretion rates (r = -0.61 and -0.69, respectively, P < 0.001) and directly related to the hematocrit (r = 0.56, P < 0.001). Renal plasma flow was disproportionately higher than GFR, so that filtration fraction was low in all groups. Albuminuria was accompanied, even in patients with normal GFR, by a reduction in ultrafiltration coefficient (16 +/- 3 in albuminuria vs. 25 +/- 3 in controls, P < 0.05). A more severe loss of ultrafiltration coefficient and glomerular permselectivity occurred in CRF. We conclude that renal failure in SSA occurs because of glomerular injury with loss of ultrafiltration coefficient and glomerular permselectivity. The earliest clinically detectable abnormality is an increase in albumin and IgG excretion. When albuminuria is present, the ultrafiltration coefficient is already diminished even if GFR is preserved. Detection of albuminuria can identify established glomerular injury in SSA.