Ticlopidine, a potent inhibitor of platelet aggregation, was found to have no direct effects on coronary resistance or coronary flow in 5 dogs. To determine whether platelets can be implicated in the pathogenesis of myocardial ischaemia the effects of this drug were studied in 10 patients with proven coronary-artery disease and daily angina pectoris. Each underwent three single-blind treatments: (a) placebo for 2 weeks; (b) ticlopidine 500 mg for 4 weeks; and (c) placebo for 2 weeks. For 4 days after the end of each treatment ambulatory S-T segments were monitored and a record was kept of the reported frequency of chest pain. 4 weeks' treatment with ticlopidine resulted in a significant fall in both the reported frequency of chest pain and the number of episodes of S-T segment depression. This effect was most striking in those episodes of S-T segment depression that occurred without increase in heart rate and in the middle of the night. Thus, although the exact mechanisms remain to be clarified this study suggests that platelets may play an important part in the pathogenesis of myocardial ischaemia.