The Ca2+-binding S100A1 protein displays a specific and differential expression in the human myocardium and is considered to be an important regulator of heart function. Because of its high expression levels in the heart we tested the performance of S100A1 as a diagnostic indicator of acute myocardial damage. Therefore, we established a S100A1-specific sandwich ELISA and determined the S100A1 plasma levels in patients with signs of acute myocardial ischemia. The concentration-time course of S100A1 was distinct from that of the "classical" biochemical markers, CK, CKMB, and troponin I, showing an early rise and a fast decline in plasma after the ischemic event. We suggest that S100A1 should be included in combinatorial measurements as an early diagnostic marker for ischemic coronary diseases.