We have suggested that among conscious dogs with a healed anterior wall myocardial infarction (MI) a depressed baroreflex sensitivity (BRS) carries a higher risk of developing ventricular fibrillation during a brief ischemic episode associated with an exercise stress test. The clinical and pathophysiological implications of our previous findings prompted the present study, which addressed three major questions: 1) Is, indeed, analysis of BRS after MI a specific and sensitive marker for sudden death-risk stratification? 2) Does MI modify BRS? 3) Does analysis of BRS before MI provide information about outcome during ischemic episodes occurring after MI? An anterior MI was produced in 301 dogs, and 4 weeks later, a 2-minute circumflex coronary artery occlusion beginning during the last minute of an exercise stress test could be performed in 192 animals. Ventricular fibrillation occurred in 106 (55%) dogs (susceptible to sudden death), whereas 86 (45%) dogs (resistant to sudden death) survived. BRS was assessed by the phenylephrine method and was expressed by the regression line relating RR intervals to blood-pressure changes. BRS was significantly lower among susceptible than among resistant dogs (9.1 +/- 6.0 vs. 17.7 +/- 6.5 msec/mm Hg, p less than 0.0001). The risk for sudden death increased from 20% (15 of 73 dogs) for a BRS greater than 15 msec/mm Hg to 91% (62 of 68 dogs) for a BRS less than 9 msec/mm Hg (p less than 0.001). An internal control study in 55 animals showed that BRS was reduced 4 weeks after MI compared with control conditions (13.5 +/- 6.7 vs. 17.8 +/- 6.6 msec/mm Hg, p less than 0.001) and that a reduction occurred in 73% of animals. Susceptible dogs and those that spontaneously died after MI had a lower BRS even before the MI (16.2 +/- 5.9 vs. 22.2 +/- 6.2 msec/mm Hg, p less than 0.001). The risk for sudden death after MI increased from 35% (nine of 26 dogs) for a BRS before MI greater than 20 msec/mm Hg to 85% (17 of 20 dogs) for a BRS before MI less than 14 msec/mm Hg (p less than 0.001). This study demonstrates that the presence of a reduced BRS is associated with a greater susceptibility to ventricular fibrillation during subsequent ischemic episodes. In the majority of dogs, BRS is reduced after an MI. The results in 192 conscious dogs with a healed MI indicate that analysis of BRS is a powerful tool for risk stratification not only after, but even before, the occurrence of an MI.