A prospective multicenter study was designed to determine the frequency and prognostic importance of hypercalciuria in children with hematuria. Urinary calcium excretion was examined in 215 patients with unexplained isolated hematuria (no proteinuria, urolithiasis, infection or systemic disorder). Hypercalciuria (urinary calcium excretion greater than 4 mg/kg/day) was identified in 76 patients (35%). Compared to patients with normal urinary calcium excretion, children with hematuria and hypercalciuria were characterized by male preponderance, white race, family history of urolithiasis, gross hematuria and calcium oxalate crystals. Renal biopsies were performed in 10 patients with urinary calcium excretion 0.4 to 2.5 mg/kg/day; three had IgA glomerulonephritis, three had glomerular basement membrane thinning, one had proliferative glomerulonephritis and three were normal. Renal biopsies in three patients with hypercalciuria showed focal segmental glomerulosclerosis, hereditary nephritis or no abnormalities. Oral calcium loading tests showed renal hypercalciuria in 26 patients, absorptive hypercalciuria in 15 patients and were not diagnostic in 35 patients. Serum parathyroid hormone, bicarbonate and phosphorus and urinary cyclic adenosine monophosphate concentrations were similar in the three groups of hypercalciuric patients. Urinary calcium excretion after one week of dietary calcium restriction was higher (5.8 mg/kg/day) in renal hypercalciuria than in other hypercalciuric patients (3.4 mg/kg/day), P less than 0.01. One to four years follow-up was available for 184 patients. Eight of 60 hypercalciuric patients developed urolithiasis or renal colic compared to 2 of 124 patients with normal urinary calcium excretion (P less than 0.001). Hypercalciuria is commonly associated with isolated hematuria and represents a risk factor for future urolithiasis in children with hematuria.(ABSTRACT TRUNCATED AT 250 WORDS)