The aim of the study was to investigate the clinical significance of additional ST-segment elevation that occurs during thrombolytic therapy. Therefore, we classified 153 patients with a first acute myocardial infarction (MI) into two groups: Group A, 55 patients with additional ST-segment elevation > or = 1 mm above the initial ST elevation during thrombolytic therapy and Group B, 98 patients without this electrocardiographic pattern. Among the patients with anterior MI, Group A (n = 33) had no reduction from ST-predicted to final QRS-estimated infarct size (+12% versus -27%; p = 0.0005) and a larger final infarct size (QRS-score: 18% versus 12%; p = 0.0002) than Group B (n = 41). Among the patients with inferior MI, Group A (n = 22) had a smaller reduction from ST-predicted to final QRS-estimated infarct size (-30% versus -53%; p = 0.03) and a larger final infarct size (QRS-score: 15% versus 9%; p = 0.03) than Group B (n = 57). The area under the curve (AUC) of CK and CK-MB was higher in patients from Group A compared with those from Group B (anterior MI: AUC-CK: 22,048 versus 19,490 U.h.l-1; p = 0.07; AUC-MB: 2227 versus 2016 U.h.l-1; p = 0.11; inferior MI: AUC-CK: 17,206 versus 11,004 U.h.l-1; p = 0.01; AUC-MB: 2193 versus 1046 U.h.l-1; p = 0.007). Both global left ventricular function and ST-segment elevation resolution were significantly better in Group B. Two and three vessel disease was observed more frequently in Group A. Additional ST-segment elevation during thrombolytic therapy suggests reduced myocardial salvage by thrombolytic therapy and thus may result in larger final infarct size.