The purpose of this study was to evaluate the sensibility of some clinical and non-invasive parameters in the early diagnosis of cardiac rejection in heart transplant patients. Eighteen patients (15 males and 3 females) aged 13-57 years (mean 44 +/- 14), with orthotopic heart transplant were followed clinically for a mean period of 15 +/- 8.7 months (range 3-27). They were all treated with cyclosporin, associated with azathioprine or prednisone, or both. During the same day of the endomyocardial biopsy, the patients were submitted to a clinical examination, 12 leads ECG and 2-dimensional and Doppler-echocardiography. The following parameters were evaluated: systolic and diastolic blood pressure, heart rate, body weight, summated QRS voltage in the 12 leads ECG, interventricular septum and left ventricular posterior wall end-diastolic thickness, left ventricular myocardial mass and fractional shortening, isovolumic relaxation time. Biopsy specimens were graded according to the Billingham criteria. Totally, 251 biopsies were performed: 130 were negative, 98 positive for mild or moderate rejection, 23 had a resolving rejection pattern; in 61 cases the patients were treated for acute rejection. Compared to negative biopsies, during acute rejection the QRS voltage and the isovolumic relaxation time significantly decreased, while left ventricular wall thickness and body weight increased. To evaluate the effects of the acute immunosuppressive therapy, the same parameters before and after treatment were compared. The QRS voltage, the wall thickness and the isovolumic relaxation time were significantly modified, returning to the pre-rejection values. In conclusion, both clinical and non-invasive information, may be useful to suspect an episode of acute rejection in heart transplant patients and to program myocardial biopsy.