['To determine the test performance characteristics of serial creatine kinase-MB (CK-MB) mass measurements for acute myocardial infarction (MI) in patients presenting to the ED with chest pain and nondiagnostic ECGs.', 'A prospective, observational test performance study was conducted. Hemodynamically stable patients aged > or = 25 years with chest discomfort, but without ECGs diagnostic for MI, were enrolled at 7 university teaching hospitals. Presenting ECGs showing > 1-mV ST-segment elevation in > or = 2 electrically contiguous leads were considered diagnostic for MI; patients with diagnostic ECGs on presentation were excluded. Real-time, serial CK-MB mass levels were obtained using a rapid serum immunochemical assay at the time of ED presentation (0-hour) and 3 hours later (3-hour). The following testing schemes were evaluated for their sensitivity and specificity for detection of MI during patient evaluation in the ED: 1) an elevated (> or = 8 ng/mL) presenting CK-MB level; 2) an elevated presenting and/or 3-hour CK-MB level; 3) a significant increase (i.e., > or = 3 ng/mL) within the range of normal limits for CK-MB concentrations during the 3-hour period (delta CK-MB); and/or 4) development of ST-segment elevation during the 3 hours (second ECG).', 'Of the 1,042 patients enrolled, 777 (74.6%) were hospitalized, including all 67 MI patients (8.6% of admissions). As a function of duration of time in the ED, the test performance characteristics of serial CK-MBs for MI (and cumulative data for the additional ECG) were: [table: see text] The 0-hour to 3-hour CK-MB positive and negative predictive values were 52% to 55% and 96% to 99%, respectively. The sensitivities of serial CK-MB results as a function of the interval following chest discomfort onset were: [table: see text]'] Are serial creatine kinase-MB results a sensitive indicator of acute myocardial infarction in chest pain patients with nondiagnostic electrocardiograms : the second Emergency Medicine Cardiac Research Group Study?