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During the healing phase of evolving myocardial infarction, inflammatory cells invade the affected region and produce metabolites that may influence electrophysiological parameters and the genesis of malignant arrhythmias. We have recently shown an increased synthetic capacity within an evolving infarct for thromboxane A2(TxA2), a metabolite that has been implicated in arrhythmias associated with early ischemia. The present study used both in vivo and in vitro procedures to define the electrophysiological and arrhythmogenic effects, if any, of thromboxane during evolving myocardial infarction. Thirty-three dogs divided into three groups were studied 3–7 days after transient left anterior descending coronary artery ligation. One group (n 24) was examined by programmed electrical stimulation in the conscious state and, of the five dogs in this group with sustained ventricular tachycardia (VT), none demonstrated consistent limitation of inducibility by selective inhibition of thromboxane synthetase using three different agents. In the second group, (n 5) regional conduction velocity was assessed using detailed three-dimensional activation analysis from 232 simultaneous intramyocardial sites, and no change was induced by the thromboxane synthetase inhibitor OKY-1581 in either normal or infarcted myocardial zones during sinus rhythm or with pacing. In the third group (n 4), isolated ventricular muscle was studied in vitro using both intracellular transmembrane action potential recordings and surface extracellular maps from 48 simultaneous points. Neither intracellular action potential parameters nor extracellulary recorded activation patterns were altered by superfusion with the stable thromboxane analog STA2, the activity of which was verified by bioassay. Thus, despite increased synthetic capacity for thromboxane generation, the presence of TxA2does not directly influence either electrophysiological indices or arrhythmogenesis.