The purpose of this study was to examine the differential myocardial signal responses due to the blood oxygen level dependent (BOLD) effect in magnetic resonance imaging (MRI) under differing conditions of myocardial oxygen supply and demand. The signal response was measured when myocardial blood flow was increased in excess of oxygen demand or when flow was increased in response to increased myocardial oxygen demand. Normal volunteers were studied using a segmented, interleaved, double-echo, gradient-echo sequence at baseline conditions and during pharmacological stress with either dipyridamole (n = 5) or dobutamine (n = 6). Changes in T2* in the myocardium during stress were calculated. Peak coronary flow velocity was measured at rest and during stress using a breath-hold phase contrast technique. Administration of dipyridamole induced a 124 +/- 27% increase in coronary blood flow which resulted in a 46 +/- 22% increase in T2*, consistent with a decrease in myocardial venous deoxyhemoglobin concentration as myocardial oxygen supply exceeds demand. In contrast, the administration of dobutamine resulted in a 41 +/- 25% increase in coronary blood flow but no significant change in T2* (-5 +/- 19%), consistent with a lack of change in myocardial venous deoxyhemoglobin concentration and balanced oxygen supply and demand. Thus, alterations in the relationship between myocardial oxygen supply and demand appear to be detectable using BOLD MRI.