The inherent imperfection of clinical diagnostic tests introduces uncertainty into their interpretation. The magnitude of diagnostic uncertainty after any test may be quantified by information theory. THe information content of the electrocardiographic ST-segment response to exercise, relative to the diagnosis of angiographic coronary artery disease, was determined using literature-based pooled estimates of the true- and false-positive rates for various magnitudes of ST depression from less than 0.5 mm to greater than or equal to 2.5 mm. This analysis allows three conclusions of clinical relevance. First, the diagnostic information content of exercise-induced ST-segment depression, interpreted by the standard 1.0-mm criterion, averages only 15% of that of coronary angiography. Second, there is a 41% increase in information content when the specific magnitude of ST-segment depression is analyzed, as opposed to the single, categorical 1-mm criterion. Third, the information obtained from ECG stress testing is markedly influenced by the prevalence of disease in the population tested, being low in the asymptomatic and typical angina groups and substantially greater in groups with nonanginal chest pain and atypical angina. The quantitation of information has broad relevance to selection and use of diagnostic tests, because one can analyze objectively the value of different interpretation criteria, compare one test with another and evaluate the cost-effectiveness of both a single test and potential testing combination.