The incremental value of clinical assessment, exercise electrocardiography (ECG) and biplane radionuclide ventriculography (RVG) in the prediction of coronary artery disease (CAD) was assessed in 105 men without myocardial infarction who were undergoing coronary angiography for investigation of chest pain. Independent clinical assessment of chest pain was made prospectively by 2 physicians. Graded supine bicycle exercise testing was symptom-limited. Right anterior oblique ECG-gated first-pass RVG and left anterior oblique ECG-gated equilibrium RVG were performed at rest and exercise. Regional wall motion abnormalities were defined by agreement of 2 of 3 blinded observers. A combined strongly positive exercise ECG response was defined as greater than or equal to 2 mm ST depression or 1.0 to 1.9 mm ST depression with exercise-induced chest pain. A multivariate logistic regression model for the preexercise prediction of CAD was derived from the clinical data and selected 2 variables: chest pain class and cholesterol level. A second model assessed the incremental value of the exercise test in prediction of CAD and found 2 exercise variables that improved prediction: RVG wall motion abnormalities, and a combined strongly positive ECG response. Applying the derived predictive models, 37 of the 58 patients (64%) with preexercise probabilities of 10 to 90% crossed either below the 10% probability threshold or above the 90% threshold and 28 (48%) also moved across the 5 and 95% thresholds. Supine exercise testing with ECG and biplane RVG together, but neither test alone, effectively adds to clinical prediction of CAD. It is most useful in men with atypical chest pain and when the ECG and RVG results are concordant.