The effects of glutamate on exercise tolerance, ischemic threshold and venous substrate concentrations were studied in 20 patients with stable angina pectoris and positive stress tests. Each patient underwent 4 upright bicycle exercise tests on consecutive days. The first and fourth tests were performed without medication while the second and third tests were preceded by a low and high bolus dose of monosodium glutamate, either 0.8 and 1.5 mg/kg body weight intravenously (10 patients) or 40 and 80 mg/kg orally (10 patients). Comparison of the first and fourth tests revealed good reproducibility of electrocardiographic, hemodynamic and metabolic data. Glutamate increased exercise duration (p less than 0.05) in a dose-related way when given intravenously (59 +/- 14 and 153 +/- 14 seconds) and when given orally (53 +/- 21 and 90 +/- 23 seconds; all data are mean +/- standard error of the mean). It also delayed the onset of ST-segment depression (p less than 0.05) by 73 +/- 19, 120 +/- 23, 62 +/- 27 and 80 +/- 30 seconds, respectively. Hemodynamics were not changed by glutamate at rest or at comparable workloads, but at onset of ST-segment depression the heart rate-blood pressure product was increased (p less than 0.05). Glutamate administration induced dose-related 1.5- to 10-fold elevations in plasma glutamate, 15 to 50% decreases in plasma free fatty acids (p less than 0.05) and 5 to 30% increases in plasma alanine contents. Circulating levels of glucose, lactate, citrate and albumin were not modified by glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)