The early release patterns of MB-creatine kinase (CK-MB) in myocardial ischemia and infarction are largely unknown. We utilized a sensitive column chromatographic assay of CK-MB activity (precision = 1.1 IU/liter) and sequential CK-MB samples were obtained during the first 6 hours of illness to define the early time course of enzyme release. The average CK-MB in 39 normal subjects was 2.4 +/- 0.93 (mean +/- standard deviation (SD)). Twenty-two patients with ischemic chest pain, in whom myocardial infarction did not develop, were characterized by normal CK-MB's (2.4 +/- 1.0). Of 39 patients in whom transmural myocardial infarction developed, 28 (72 percent) were found to have abnormal CK-MB either initially or over a 20-minute sampling period. In contrast, 100 percent of the patients considered to have sustained a nontransmural myocardial infarction had abnormal initial CK-MBs and subsequently demonstrated significant increases in CK-MB from 28 +/- 19 initially to 41 +/- 30 IU/liter (P less than 0.01, N = 16) over the 20-minute sampling period. Thus, CK-MB appears earlier in plasma following nontransmural myocardial infarction than transmural myocardial infarction, probably reflecting perfusion to ischemic myocardium.