Two divergent laboratory approaches to the measurement of lactate dehydrogenase (LD) isoenzymes (LDIs) were evaluated. Abnormal values for total creatine kinase (CK), CK-MB, total LD, and LDIs were greater than 250 U/L, greater than or equal to 5% total CK, greater than 180 U/L, and LD1/LD2 ratio greater than 1.0, respectively. The first approach, measuring LDI on all requests regardless of total LD activity, showed the following results: 161 LDI specimens, 63 CK-MB + (LD1 greater than LD2, 6; LD1/LD2 normal, 57); 98 CK-MB - (LD1 greater than LD2, 5, LD1/LD2 normal, 93). Medical chart review of the 98 CK-MB negative specimens, representing 44 patients, showed that in seven patients with acute myocardial infarction (MI), none would have been missed clinically even if LDIs had not been done, and in only one case did LDIs play a confirmatory role in a patient who persistently had CK-MB-negative results but who had a strong clinical suspicion of MI. None of the 42 patient specimens with normal total LD activity had an LD1 greater than LD2. The second approach, measuring LDIs only if requested, only if total CK was abnormal, only if results for CK-MB were negative, and only if total LD was abnormal, showed the following results: 71 LDI specimens were not done (46 with normal total LD, 25 CK-MB + specimens). Medical chart review of the 71 LDIs not determined, representing 38 patients, showed that none of the 14 patients with the final diagnosis of MI would have been clinically missed, even if LDI had not been done, and in only one instance did LDIs confirm the clinical suspicion of MI in a patient with previously negative results for CK-MB. The LDI protocol represented by the second approach has been shown to be an effective means of identifying those occasional patients who require this confirmatory test, in whom the CK-MB results are negative but in whom there is a strong clinical suspicion of MI.