1. Changes in the urine/plasma (U/P) or urinary concentrations of creatinine, urea and phenacetin and its main metabolites, p-acetamidophenol (paracetamol) and p-phenetidine (p-ethoxy aniline), were determined during the transition from water diuresis to vasopressin-mediated antidiuresis in normal subjects given phenacetin (30–45 mg/kg). Studies were performed during both acid (NH4Cl) and alkali (NaHCO3) loading.
2. The U/P ratio of urea, phenacetin and p-acetamidophenol and the urinary concentration of p-phenetidine rose less than that of creatinine during both acid and alkali loading, indicating increased reabsorption of these compounds during vasopressin activity.
3. The mechanism by which phenacetin and its metabolites may cause renal papillary necrosis are discussed.