Patients with nephrotic syndrome (NS) are at increased risk for infection. Peritonitis is difficult to diagnose in the absence of peritoneal fluid analysis and empiric therapy carries significant risks. We identified factors present at initial presentation that are associated with an increased risk for the later development of spontaneous bacterial peritonitis in children with NS. A case-control study of patients admitted to Children's Hospital and Regional Medical Center, Seattle from 1989 to 1999 with a diagnosis of NS was conducted; 8 cases of NS and peritonitis (aged 20-113 months) and 24 controls with NS alone (aged 10-193 months) were identified and matched on year of diagnosis of NS. Medical charts were reviewed and laboratory values at the time of initial presentation of NS were recorded. Odds ratios (OR) were estimated, Fischer's exact test was used to obtain P values, and 95% exact confidence intervals (CI) were also calculated. Cases tended to be younger than controls (mean age 50.5 months vs. 65.3 months), and were more likely to be white and male. There was a suggestion of an association between serum albumin level at presentation and the risk of subsequent peritonitis. Those patients with a serum albumin level less than or equal to 1.5 g/dl at initial presentation were estimated to have a 9.8-fold (95% CI 0.93, 472; P=0.06) increase in the odds of developing peritonitis than those with an initial albumin greater than 1.5 g/dl. A platelet count greater than 500 cells/mm(3)tended toward a reduced risk (OR=0.12, 95% CI 0.002,1.29; P=0.10) for subsequent peritonitis when compared with patients with a platelet count less than 500 cells/mm(3), but was not statistically significant. Hypertension, hematuria, or normal serum complement levels (C3, C4) at the time of initial diagnosis were not associated with an increased risk of subsequent peritonitis. Low serum albumin (< or = 1.5 g/dl) at presentation was associated with an increased risk of peritonitis among children with NS at our institution.