Background Acute rejection may be suspected in heart transplant recipients in the setting of new onset of clinical symptoms or alterations in cardiac function.Immediate diagnosis may be obtained by performing a frozen section on endomyocardial biopsy (EMB) specimens. However, little is known about the indications for, and the diagnostic reliability of, this procedure.45 days; n=51) posttransplant periods.Frozen section diagnoses (x=1.5 EMB samples) were compared with corresponding permanent section diagnoses (x=4.4 EMB samples), and clinical indications were analyzed. Comparison of frozen and permanent section interpretation revealed concordant pathological processes--rejection (n=31) versus no rejection (n=37) versus ischemic injury (n=20)--in 88 of 98 (90%) cases. Discordant pathological processes on frozen versus permanent section in 10 of 98 (10%) cases could be attributed to ischemic injury (n=5), sampling (n=4), and infection (n=1). In the 92 cases with defined clinical indications, the indication and number of EMBs positive for rejection early and late after transplantation were arrhythmia: 2 of 12 early, 4 of 10 late; congestive heart failure: 1 of 2 early, 5 of 12 late; fever: 0 of 2 early, 1 of 4 late; echo abnormality: 0 of 5 early, 0 of 1 late; syncope: 1 of 5 early, 0 of 1 late; hypotension: 1 of 3 early, 1 of 2 late; noncompliance: 0 of 0 early, 4 of 5 late; more than one of the above: 3 of 7 early, 2 of 5 late; other: 1 of 7 early, 1 of 9 late; total: 9 of 43 early, 18 of 49 late.Conclusions Frozen section on EMB specimens accurately reflected the permanent section diagnosis in 90% of cases.No specific clinical indication predicted EMB rejection positivity with high sensitivity in either the early or late posttransplant periods. (Circulation. 1994;89:2079-2084.)