Asthma is an inflammatory disease involving the airways. E-series prostaglandins have potent anti-inflammatory effects on neutrophils and T lymphocytes. Accordingly, we tested the acute (i.e., 6 h) and chronic (i.e., 1 week) effects of oral misoprostol 200 &mgr;g in five stable asthmatics. A double-blind, randomized, crossover design was used. Airway function was assessed from measurements of forced expiratory volume in 1 s (FEV(1)). The number of puffs of the inhaled beta-adrenergic agonist bronchodilator, albuterol, taken for symptomatic rescue, was assessed by diary. FEV(1) measured serially for 6 h after 200 &mgr;g misoprostol was similar on misoprostol and placebo days in all subjects. In contrast, three of the five subjects showed appreciable increases in FEV(1) during a week of misoprostol compared to either baseline or placebo week. Two subjects showed no change in the FEV(1) with 1 week of misoprostol. All three of the subjects who kept a diary decreased the number of puffs of albuterol during the misoprostol compared to placebo period. Of note, in these three subjects, airway function improved (n = 1) or remained the same (n = 2) despite a diminution in the number of puffs of a beta-agonist administered. None of the subjects administered the 200-&mgr;g oral dose QID reported any significant symptoms or adverse reaction. In conclusion, several inferences can be drawn from this early preliminary study. These data suggest that a trial involving a large number of subjects, a longer period of treatment, and a more objective method of assessing inhaler use may be useful in evaluating the chronic effects of misoprostol in asthma.