Arteriovenous differences (A-V) of all naturally occurring amino acids, lactate, and oxygen were measured simultaneously with coronary sinus blood flow (CSBF) in 8 normal subjects and 11 patients with coronary artery disease at rest and during pacing stress. Mean values for CSBF and myocardial oxygen consumptions (MVO2) for the two groups were similar at rest and during pacing, although mean CSBF and MVO2 increased significantly in both groups in the paced as compared to the rest state. Alanine (ala) was the only amino acid released by the myocardium, while only glutamic acid(glu) demonstrated uptake. Mean A-V ala was negative at rest in the control and coronary disease groups (-4.8+/-3.8 vs. -22.0+/-3.0 nmol/ml, respectively), but was significantly more negative in the coronary group (P less than 0.001) and not statistically different than zero in the normals. A-V ala became significantly negative with pacing in the normals (-10.0+/-4.3 nmol/ml), remained unchanged in the coronary group (-23.0+/-2.9 nmol/ml), and was significantly more negative in the coronary group (P less than 0.05). Calculation of data on the basis of net ala flux ([A-V] X [CSBF X hematocrit]) yielded similar results as that obtained with A-V differences. A-V glu was significantly positive in normals (27.7 +/- 8.9 nmol/ml, P less than 0.01) and coronary patients (59.9 +/- 8.9 nmol/ml, P less than 0.01) at rest but significantly greater in the latter group (P less than 0.001). With pacing, A-V glu remained significantly greater than zero in coronary patients (35.3 +/- 6.3 nmol/ml) and decreased to zero in the normals (4.3 +/- 11.8 nmol/ml). Calculation of net glu flux (nmol/min) at rest yielded data similar to that based on A-V difference. With pacing, net glu flux in the coronary patients did not decrease due to the augmentation of CSBF. No relation between A-V glu or ala and CSBF, MVO2 or A-V lactate was noted. The data demonstrate that specific alterations of myocardial amino acid metabolism characterize patients with chronic ischemic heart disease.