Aquaporin-2 protein levels can be detected in the urine of normal of subjects if measured after fluid deprivation. By contrast, in patients with nephrogenic diabetes insipidus caused by mutations in the aquaporin-2 gene, urine aquaporin-2 protein excretion cannot be detected. We propose that properly standardized measurements of urinary aquaporin-2 protein may provide a useful biomarker of distal tubular function in a variety of acquired conditions that impair concentrating ability including some nephrotoxic agents.