Echocardiographic quantification of myocardial perfusion after IV contrast is possible, based on the intensity of the received intermittent second harmonic signal. To investigate the influence of respiration on the intensity of myocardial signals, we examined nine patients with normal coronary angiograms. At baseline, end-expiratory and end-inspiratory images were obtained in broadband radiofrequency (RF) and intermittent second harmonic modes, the latter repeated during IV contrast at rest and at peak stress. In mid-septum at baseline, end-inspiratory integrated backscatter intensity was 4 dB higher (p < 0.05, both in second harmonic and fundamental domains) than end-expiratory intensity. In second harmonic imaging, contrast increased signal intensity by 4 dB (p < 0.05) in six examined segments, but the increase in the midseptal region (2 dB) was not significant. Contrast-enhanced intensity at end-inspiration was higher (3 dB, p < 0.01) than baseline intensity at end-expiration. We conclude that the increase in myocardial signal intensity during inspiration may resemble the contrast effect in intermittent second harmonic mode. The respiratory variation persists after contrast and may mask or exaggerate the effect of myocardial contrast.