The authors prospectively compared the ability of Tc-99m pyrophosphate (PYP) and Tc-99m methylene diphosphonate (MDP) to detect acute myocardial infarctions. The agents used were PYP (12 mg) with 3.4 mg of stannous chloride, MDP (10 mg) with 1.0 mg of stannous chloride, and MDP (10 mg) with 3.4 mg of stannous chloride. Imaging was performed on three consecutive days on 34 patients with proven myocardial infarctions, using the same agent on the first and third days of the study and an alternate agent on the second day. Agents were assigned randomly to each of six groups of patients. First images were obtained an average of 3.7 days (range, one to six days) following myocardial infarction. Seventeen of 23 patients (75%) had images positive for acute myocardial infarction with Tc-99m PYP, whereas only two of 21 patients (9.5%) had positive studies with Tc-99m MDP with 3.4 mg of stannous chloride and one of 24 patients (4.2%) had positive studies with Tc-99m MDP and 1.0 mg of stannous chloride. All three myocardial infarctions detected by Tc-99m MDP were extensive and transmural. When MDP and PYP were both positive in the same patient, the apparent size of the myocardial infarction was much smaller with the MDP. It is concluded that MDP can detect only large myocardial infarctions, has poor localization in the infarcted tissue, and varying the stannous chloride content of the preparation does not improve the ability of MDP to detect acute myocardial infarctions.