Persistent proteinuria without edema, associated with focal segmental glomerulosclerosis (FSGS), has been increasingly observed in our pediatric population. The clinical and pathological features and long-term outcome of these patients are poorly understood and less frequently reported. Ten nonedematous children (10.3 +/- 1.4 years) with proteinuria and FSGS are compared with 16 children (9.0 +/- 0.4 years) with FSGS and nephrotic syndrome (NS). Urinary protein excretion and serum cholesterol were statistically higher and serum albumin statistically lower in the children with FSGS-NS. The percentage of glomeruli with sclerosis was similar in the two groups. Mesangial proliferation was observed more frequently in the nephrotic children and focal or diffuse tubular atrophy more often in the nonedematous children with FSGS. Followup serum creatinines are more than 1 SD above the mean for age in 3 of 10 nonedematous patients with FSGS and 9 of 16 patients with FSGS-NS. Of 10 nonedematous patients with FSGS, 1 progressed to renal failure 20 months after diagnosis, while 3 of 16 patients with FSGS-NS progressed to renal failure. We conclude from these data that NS is a poor prognostic sign in FSGS in children and that neither the percentage of glomeruli with sclerosis nor the presence of tubular atrophy is predictive of NS in our patients.