Reproducibility of myocardial ischemia induced by atrial pacing (P) was investigated in 25 patients (pts) without previous anterior myocardial infarction and showing a positive exercise stress test. The second period of atrial pacing (P2) was exerted 20 minutes after the first (P1). During P2, a reduction in the parameters reflecting myocardial oxygen requirements (maximal left ventricular pressure, dp/dt max, TTI*HR values) was noted, while the signs of ischemia were less pronounced (ST depression decreasing from 2.3 +/- 1 mm to 1.6 +/- 1.0 mm; % of lactate extraction (%L) decreasing from - 6.4 +/- 25.5 to + 8.5 +/- 19.2; p less than 0.5). The 25 pts were divided into 2 groups according to the ejection fraction (EF greater than .55 16 pts Gr.F+; EF less than .55 9 pts Gr.F-). The distribution of coronary lesions was the same for the 2 groups. During P1 GR.F+ registered a negative % L as opposed to Gr.F-. During P2, the difference in the % L between the 2 groups was also significant (2.6 +/- 19.9% F+ vs 18.9 +/- 14.3% F-; p less than .05). Collateral circulation had no effect upon the results, neither for P1 or P2. This study shows that a second period of atrial pacing, 20 minutes after the first, induced lesser ischemia than the first period of atrial pacing. This phenomenon could explain the paradoxical improvement observed in certain patients after a first episode of angina. These results have implications as regards the necessity of double blind studies compared to placebo when using this technique in the evaluation of the effects of anti-ischemic drugs.