To test the hypothesis that single-photon emission computed tomography (SPECT) of 99mTc-pyrophosphate (99mTc-PPi) with and without the overlay of tomographic blood pool scintigrams might detect small infarcts not identified by planar imaging, 52 patients were studied 3.2 +/- 2.0(SD) days after hospital admission for suspected acute myocardial infarction. Patients were chosen prospectively for tomographic study primarily, but not exclusively, because planar four-view imaging with 99mTc-PPi was either negative or equivocal. SPECT was performed with a commercial rotating detector system immediately after planar imaging on one occasion. Corresponding 99mTc-PPi and blood pool sections were mapped into opposite halves of a bichromic color table and displayed as an overlay. Planar images, SPECT and SPECT with blood pool overlay were interpreted separately and in random order without knowledge of clinical data. Seventeen patients had transmural infarcts (four anterior, 13 inferior), 19 had nontransmural infarcts, and 16 patients did not have acute myocardial infarction. The sensitivity of SPECT with blood pool overlay was significantly better than planar imaging for the entire group with myocardial infarction (97% vs 78%; p less than .025); this was primarily due to increased sensitivity in the detection of nontransmural myocardial infarction (95% vs 67%; p less than .05), although in one additional patient inferior transmural myocardial infarction was also detected by the SPECT overlay technique. The specificities of the SPECT overlay technique and planar imaging were not significantly different; however, receiver operating characteristic analysis showed enhanced observer confidence with the tomographic method. SPECT without overlay was intermediate in sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)