Fractional excretion (FE) of beta 2 microglobulin (beta 2M) was studied in children with glomerular (N = 114), tubular (N = 50) or other (N = 18) renal diseases. FE-beta 2M (normal less than 0.36%) was significantly (P less than 0.001) lower in glomerular diseases (mean 0.104%) than in tubular lesions (mean 4.27%). Unexpectedly, several patients with glomerular disease were found to have increased values for FE-beta 2M. To determine whether this was due to a tubular component in a primary glomerular disease process, FE-beta 2M was measured in 30 children with various glomerulopathies who underwent renal biopsy. Thirteen of these patients had tubulo-interstitial lesions in addition to their glomerular disease. FE-beta 2M in these patients averaged 3.76% (range 0.14 to 44.6%); only two results were normal. Mean FE-beta 2M in the 17 patients without biopsy evidence of tubulo-interstitial disease was 0.063% (range 0.02 to 0.34%); all values were in the normal range. The types of glomerular diseases in the two groups of patients were similar. Patients with a glomerular lesion complicated by tubulo-interstitial lesions had a poorer prognosis than did those with a pure glomerular disease. The high incidence of tubulo-interstitial lesions in patients with glomerular diseases was unexpected. Our data demonstrates that FE-beta 2M represents a reliable non-invasive method to diagnose such involvement. Measurements of beta 2M also provide a convenient method to follow the course and response to treatment of renal tubular injury.