The N-acetyl-beta-D-glucosaminidase (NAG) activities and albumin levels in the urine of 32 patients with active rheumatoid arthritis treated with low-dose pulse methotrexate (MTX) have been investigated. An increase in NAG urinary excretion was more frequent than the incidence of micro- or macroalbuminuria on entry, and during treatment with MTX. There was also a significant decrease in NAG levels observed at week 24. Parameters such as patient's age, time from onset, previous and current treatment did not allow us to predict the degree of NAG enzymuria. We conclude that MTX does not cause marked damage to renal proximal tubules; on the contrary, the observed significant decrease of urinary NAG on week 24 could be interpreted as a beneficial effect of MTX on kidney function. Early detection of high NAG enzymuria and elevated albumin levels in urine before the initiation of MTX therapy could be helpful in predicting possible MTX toxicity probably related to impaired renal clearance of MTX. Patients withdrawn from the study for non-renal-related adverse events also had an unusually large increase in urine NAG activity and urine albumin levels.