Acute rejection of the donor heart is a major cause of mortality in infant heart transplant recipients. The early diagnosis of acute cardiac rejection (ACR) is crucial. Non-invasive methods have shown poor sensitivity in detecting rejection when compared to endomyocardial biopsies (EMB). We assessed troponin I as a new marker to diagnose cardiac rejection. Serum cardiac troponin I (cTNI) levels were retrospectively analysed in 25 heart transplant patients (ages, 2 wk to 13 yr; mean age, 3 months) presenting 36 acute rejections. In early post-operative rejection and initially elevated cTNI levels, rejection was associated with a second increase of serum cTNI concentrations in 21% of the patients (p = 0.15). If cTNI levels were in normal range before ACR an elevation was monitored in 59% of the rejection periods (p < 0.05). In 25% of the cases (n = 9) cTNI levels remained in normal range during the rejection episode (<0.6 ng/mL), in 22% (n = 8) cTNI levels did not exceed pathological values from 0.6 to 1.5 ng/mL and in 53% (n = 19) the measured levels went beyond 1.5 ng/mL. Maximum concentrations of cTNI were measured mostly 12 d from the moment rejection was suspected (day 1) in patients (median day 3). However, cTNI levels were elevated for 2-43 d after ACR was diagnosed (median 10 d). Twenty per cent of the patients with grade 3 rejection (ISHLT) and 75% of the patients with grade 4 rejection had a corresponding elevated cTNI level (p = 0.013). No false-positive elevations of cTNI were documented. The present data demonstrate that cTNI is a not a sensitive but a specific marker of ACR in children.