The extremely prominent negative U wave occasionally appears during a cardiac attack in variant angina pectoris. The clinical profile of the negative U wave was therefore studied in 80 patients with variant angina pectoris (VA) and 33 controls with resting angina pectoris (RA). The prominent negative U wave appeared in 55 of the patients with VA (68.8% of patients) and in 10 of the patients with RA (30.3%); thus, there was a significant difference in the appearance of the wave between the 2 groups of patients (p less than 0.001). The leads in which the negative U wave appeared were mostly consistent with those in which the ST segment was elevated. The negative U wave began to appear at about the time when ST-segment elevation began to improve; the wave then gradually became very prominent and then eventually disappeared. The patients with VA and also those with RA on whose ECGs the negative U wave appeared during exercise testing also had negative U waves during spontaneous episodes of angina. An investigation of the frequency of appearance of ST deviation and negative U waves during exercise testing, regardless of the type of angina pectoris, disclosed that the negative U wave appeared in 14 of 20 patients with ST-segment elevation (70% of patients), while the negative U wave appeared in only 52 of 519 patients with either no ST change or ST-segment depression (10.4%); thus, there was a significant difference in the appearance of the negative U wave between these 2 groups (p less than 0.001). Coronary cinearteriography failed to disclose any apparent difference between the appearance of the negative U wave and the presence of stenosis. The prognosis of VA and RA in patients with negative U waves was less favorable compared to those without negative U waves. In particular, we noted that of the 10 patients with RA associated with negative U waves, 4 died. Although the mechanism of the negative U wave is not yet known, we believe that the above findings contribute to its elucidation.