The purpose of this study was to validate different scintigraphic approaches for assessing acute myocardial infarctions. 201Tl, 99Tcm pyrophosphate (PPi) and combined 201Tl/99Tcm PPi tomograms were evaluated in 115 consecutive patients, in 85 of whom clinical examination revealed acute myocardial infarction. The overall sensitivity and specificity for infarct detection was 80% versus 56% for 201Tl alone, 61% versus 97% for 99Tcm PPi alone, and 100% each for the combined 201Tl/99Tcm PPi imaging. The sensitivity for nontransmural infarcts was 57% for 201Tl, 37% for 99Tcm PPi and 100% for combined imaging. The overlay of 201Tl and 99Tcm PPi images increases the observer's confidence in the diagnosis and provides better localization of the infarction. 201Tl alone could localize the infarction in 80%, 99Tcm PPi alone in 49% and 201Tl/99Tcm PPi in 100% of the cases. ECG and 201Tl/99Tcm PPi tomography concurred upon infarct localization in 98% of the patients. Based on the 201Tl/99Tcm accumulation pattern, 94% of the Q-wave infarctions were judged to be transmural and 83% of the non-Q-wave infarctions were judged to be nontransmural. It is concluded that combined 201Tl/99Tcm PPi tomography is highly accurate for determining the presence and location of acute myocardial infarction. This technique appears to be superior to studies where only one radioisotope is used.