Prostaglandins E2 and F2 alpha in the menstrual fluid from 12 patients with primary dysmenorrhea were measured by radioimmunoassay (RIA). Each patient was studied for 3 cycles, using vaginal tampons issued for this study. All tampons were collected individually for prostaglandin extraction and RIA. Severity of dysmenorrhea and clinical response to treatment were evaluated by a scoring method and by the patients' self-assessment. Each patient in this double-blind cross-over study had a control cycle and 2 treatment cycles with naproxen sodium tablets (275 mg) or placebo in random order. The treatment regimen was 2 tablets at the first sign of menses followed by one tablet 4 times daily for 3 days. Nine patients obtained good to excellent relief from naproxen sodium, but no relief from the placebo. Two patients had moderate to good response to both naproxen and placebo, and one patient showed no response. Naproxen therapy but not placebo therapy sharply reduced menstrual prostaglandin F2 alpha and prostaglandin E2 release. There was a positive correlation between menstrual prostaglandin levels and the severity of dysmenorrhea. Symptomatically, naproxen sodium was most effective in alleviating severe menstrual cramps but had little effect on mild cramps. It was also effective in ameliorating many but not all of the subjective symptoms such as dizziness, nausea, and vomiting. Relief of dysmenorrhea was apparent within one hour after the initial dose, attained maximum level in 2 hours, and was maintained throughout therapy.