In 50 patients with chronic stable angina and in 10 asymptomatic young male volunteers, the behavior of S-wave amplitude was studied during episodes of ischemic ST-segment depression, both induced by exercise testing and occurring during ambulatory electrocardiographic monitoring. With exercise, all patients showed diagnostic ST-segment depression (0.16 +/- 0.05 mV) which, in 49, was associated with an increase in S-wave amplitude. No consistent changes in R-wave amplitude were observed. S-wave amplitude also increased in all control subjects during exercise, but the sum of R and S wave remained constant, while it increased in 42 patients. In the 10 study patients undergoing Holter monitoring we identified 170 episodes of ischemic ST-segment depression, of which 169 were associated with increased S-wave amplitude. Isolated increases in S-wave amplitude without ST-segment changes occurred in 3 of 4 normal subjects. Dipyridamole echocardiography revealed regional wall motion abnormalities in 12 of 21 patients; the changes were invariably associated with increased S-wave amplitude but not necessarily with diagnostic ST-segment depression. An increase in S-wave amplitude is almost invariably associated with subendocardial ischemia, sometimes in the absence of ST-segment changes; this sign could represent a sensitive (although less specific) additional marker of myocardial ischemia.