The clinical usefulness of serial assays of urinary N-acetyl-β-D-glucosaminidase (NAG), γ-glutamyltransferase (GGT) and β2-microglobulin (β2M) were tested to evaluate and follow up the nephrotoxicity resulting from the prolonged administration of ciclosporin (CS). Three groups of patients were studied for 18 months: group A: functioning renal transplant patients (n = 13) on maintenance therapy from 12-31 months with CS and prednisone; group B: functioning renal transplant patients (n = ll) treated with prednisone and azathioprine; group C: patients (n = 10) affected by autoimmune steroid-unsensitive uveitis, free from previous renal disorder and treated with CS (for 8-16 months) at progressively decreasing doses. In groups A and B, the urinary enzymes and β2M underwent overlapping increases, so that these parameters cannot be considered reliable indices of CS-induced nephrotoxicity. This is due to the fact that transplanted kidneys are already altered by concomitant or preexisting affections, or by persistent immunologic injury. Conversely, in patients with uveitis, the serial assays of such urinary parameters prove to be quite reliable to evidence clinically yet unrecognizable kidney involvement due to prolonged CS administration. High enzymuria has been shown to be an earlier marker of nephrotoxicity only in nephropathy-free patients; on the other hand, the regression of elevated β2Muria into normal ranges indicates complete tubule cell rec