Patients who cannot be separated from mechanical ventilation (MV) after an episode of acute respiratory failure often have coexisting coronary artery disease. The authors hypothesized that increased left ventricular (LV) wall stress during periods of spontaneous ventilation (SV) could alter myocardial perfusion in these patients. Using thallium-201 (201TI) myocardial seintigraphy, the authors studied the occurrence of myocardial perfusion abnormalities during periods of SV in 15 MV-dependent patients (nine women, six men; aged 71 ± 7 yr, mean ± SD). Fourteen of these patients were studied once with 201TI myocardial seintigraphy during intermittent mechanical ventilation (IMV) and again on another day, after at least 10 min of SV through a T-piece. One patient was studied during SV only. Thirteen of 14 of the patients (93%) studied during MV had abnormal patterns of initial myocardial 201TI uptake, but only 1 patient demonstrated redistribution of 201TI on delayed images. The remainder of the abnormalities observed during MV were fixed defects. SV produced significant alterations of myocardial 201TI distribution or transient LV dilation, or both, in 7 of the 15 patients (47%). Four patients demonstrated new regional decreases of LV myocardial thallium concentration with redistribution of the isotope on delayed images. The patient studied only during SV also had myocardial 201TI defects with redistribution. Five patients (3 also having areas of 201TI redistribution) had transient LV dilation during SV. The change from MV to SV was accompanied by increased spontaneous minute ventilation (3.5 ± 2.6 to 8.4 ± 3.7 1/min) and mean arterial blood pressure (90 ± 2 to 98 ± 3 mmHg), and decreased pHa (7.41 ± 0.02 to 7.37 ± 0.03) (P < 0.05 by paired t test for each comparison); the Pao2, Paco2, heart rate, 12-lead ECG, tidal volume, vital capacity, and maximum inspiratory pressure were unchanged. The frequent occurrence of new regions of altered myocardial 201TI uptake and LV dilation during SV suggests that myocardial perfusion often is altered and myocardial ischemia may be present during SV in MV-dependent patients.