Buck and co-workers presented the hypothesis that the initiating factor of stone formation triggers the mechanisms for prostaglandin synthesis, resulting in the biochemical abnormalities associated with stone disease. In order to test this hypothesis, we undertook a clinical study with the use of a highly purified preparation of ethyl icosapentate. Ethyl icosapentate (1,800 mg/day) was administered to 57 patients with urinary stones chiefly composed of calcium oxalate for 6 weeks. Urinary calcium in the hypercalciuric patients reduced significantly, but the calcium level in the normocalciuric group did not decrease. Oxalate values did not reduce either in the hypercalciuric patients or in the normocalciuric subjects. No serious side effects were observed.