The efficacy of naproxen, a potent prostaglandin synthetase inhibitor, in migraine prophylaxis was assessed in a double-blind placebo-controlled cross-over study in 28 migraine patients. After a drug-free interval of at least 2 months, placebo and naproxen were given for 6 weeks each, with an interposed placebo week in between the two treatment periods. The dose of naproxen was 250 mg b.i.d. Naproxen seems to exert a moderate, but significant beneficial effect, with regard to headache days as well as headache indices. In a direct comparison, a significant number of patients preferred naproxen to placebo. Side effects were negligible. A systematic search for substances with antimigrainous properties should be made among the nonsteroidal, anti-inflammatory group substances.