Urinary and serum lactic dehydrogenase (LDH), its isoenzymes and alkaline phosphatase (AP) activities were determined for children with known nephrotic syndrome (NS) (no. = 31) and for normal controls (no. = 35 for urine, no. = 56 for serum). Patients with NS were grouped as being in relapse, in remission without prednisone, in remission for greater than 21 days with prednisone therapy, or in remission for less than 21 days with prednisone therapy. The relapse group had significant elevations of urinary LDH and AP when compared with each of the other groups. The highest urinary LDH values were seen in the relapse group, and the lowest in normal controls. The groups in remission had intermediate values of urinary LDH, which decreased as the length of time in remission increased. Although urinary AP activities were elevated in patients in relapse, they were subnormal in patients in remission greater than 21 days with prednisone therapy, suggesting membrane stabilization with resultant reduction in enzyme release into the urinary tract. The urinary and serum LDH isoenzyme patterns in the relapse group did not resemble each other, indicating the increased urinary activity was not due solely to renal clearance of serum enzymes. Serum LDH was elevated in the relapse group (P < 0.01), but it was not statistically different in the remission group when compared with controls. This study demonstrated increased urinary LDH, AP and serum LDH activities in patients with the relapsed NS. In relapsed patients, the different serum and urine LDH isoenzyme patterns suggest that the urinary activity may be a result of diseased renal tissue and not a reflection of increased glomerular filtration. Monitoring the urinary LDH activity may allow for detecting the continuing disease at a time when other clinical signs have normalized.