The effects of a commonly used non-steroid anti-inflammatory drug (naproxen) on zinc metabolism was studied in healthy volunteers. A significant increase in the urinary zinc excretion rate was found during treatment with naproxen, with a mean increase in the order of 35%. At the end of the treatment period the urinary zinc excretion fell towards normal, and after withdrawal of naproxen the urinary excretion rate became normal. During the treatment period the serum zinc concentration was virtually unchanged, being comparable to the initial and post-treatment values. The mechanism by which naproxen induces hyperzincuria is not known. Protein binding interaction or a direct renal action of naproxen implying a decrease in the maximum tubular reabsorption capacity (Tmax) would lead to an increase in zinc excretion. Prolonged studies in patients with rheumatoid arthritis, both untreated and treated with prostaglandin inhibitors, are needed however in order to evaluate the possibility of a zinc depletion.