The relationship between inverted U wave in leads V5 and II and the location of myocardial ischemia was studied in 52 positive patients and in 50 negative patients with ergonovine provocation test. Development of a biphasic or negative U wave, or increased negativity of U wave (inverted U wave) was observed in 15 of 17 patients with spasm in only the right coronary artery (RCA), in 6 of 8 with spasm in only the left anterior descending artery (LAD), in 2 of 8 with spasm in only the left circumflex artery (LCx), and in 23 of 24 with spasm in two or more vessels. Of 52 positive patients in the ergonovine provocation test, 46 (88.5%) had inverted U wave. Of these, 17 (32.7%) had inverted U wave without discernible ST deviation. Of 50 negative patients, 2 had inverted U wave. Inverted U wave in lead V5 was frequently seen in patients with spasm of LAD, but this finding was not uncommon in spasm of RCA or LCx. On the other hand, inverted U wave in lead II was frequently seen in spasm of RCA and LCx, but not in spasm of LAD. These findings suggest that inverted U wave in lead V5 is not specific for myocardial ischemia due to spasm of LAD and that inverted U wave in lead II is specific for spasm of RCA and LCx.