Twenty-one patients surviving orthotopic cardiac transplantation were studied by serial M-Mode and cross-sectional echocardiography on the same day as endomyocardial biopsy (EBS) (n = 205) during a mean follow-up period of 7.7 +/- 6 months. Results of EBS and the corresponding echocardiograms were divided into three groups: (1) no rejection (62 patients); (2) onset of mild rejection (11 patients); (3) onset of moderate rejection (17 patients). Groups 1 and 3 differed significantly in interventricular septum plus posterior wall thickness (IVS + PWth) (P less than 0.001), LV mass (P less than 0.001), LV ejection fraction (LVEF) (P less than 0.001), increased myocardial echogenicity (ME) (P less than 0.01), impaired RV wall motion (P less than 0.001). Groups 1 and 2 differed significantly only in increased ME (P less than 0.01). Groups 2 and 3 differed significantly in IVS + PWth (P less than 0.05), LV mass (P less than 0.01), LVEF (P less than 0.01), and impaired RV wall motion (P less than 0.01). With acute rejection we observed (1) increase of greater than 4 mm in IVS + PWth (55%), (2) increase of greater than 30% in LV mass (34%), (3) reduction of greater than 10 points in LVEF (27%), (4) RV dilatation and wall motion impairment (31%), (5) appearance or marked increase of pericardial effusion (34%), (6) increased ME (58%). Specificity of the individual criteria ranged from 95.6% to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)