Eighty volunteers were studied to determine the effects of 750 or 1000 mg naproxen daily for a week on intestinal permeability, by means of the 51Cr-ethylenediaminetetraacetic acid (EDTA) absorption test. With 750 mg naproxen (n = 42) the median urinary excretion increased from 2.44% to 3.51% (p less than 0.01), and with 1000 mg (n = 38) from 2.26% to 3.39% (p less than 0.01). When the individual pretreatment absorption was included in the analysis, a statistically significant difference was found between the two doses (19% and 68% median increase as a percentage of base line, respectively (p = 0.04)). Similar results were found in 27 subjects who were given both doses of naproxen. Intraduodenal instillation of the test dose in 18 subjects showed that gastric absorption was negligible, and no correlation was found with upper endoscopy findings, changes in orocoecal transit time, or reported symptoms.