A design is descirbed of a modified placebo-controlled double-blind clinical trial procedure. The design was evolved in attempt to overcome certain problems inherent in the conventional double-blind procedure, in particular the ethical problem of prolonged exposure of the patient to placebo treatment. The modified designs consist of two phases. In the first (open) phase, patients selected according to the normal protocol requirements are given the medication under study for a predetermined time. Patients responding favorably to such treatment then enter a second (double blind) phase during which is tested the null hypothesis that all the favorable effects observed during the open phase are placebo effects. Experience with this clinical trial design in the evaluation of an antianginal agent is briefly described. In this case, the null hypothesis was disproved, and a potent therapeutic action was evidenced.