The utilization of biomarkers to assess DXR cardiotoxicity has been of limited value. The present study attempts to determine whether monitoring serum levels of the cardiac protein troponin T (TT) might be useful in detecting DXR cardiotoxicity. Spontaneously hypertensive rats (SHR) were treated weekly with 1 mg/kg DXR (N=6) or saline (N=6). TT levels were determined after cumulative doses of 2, 4 and 7 mg/kg DXR. Compared with values of 0.01 ± 0.01 (ng/ml ± S.D.) in control SHR, serum levels were significantly elevated to 0.11 ± 0.03 in SHR after 7 mg/kg DXR, but not after either 2 (0.01 ± 0.01 ng/ml) or 4 mg/kg (0.02 ± 0.02 ng/ml). Loss of TT from myocytes was confirmed by confocal microscopy. Levels of TT in supernatant fluid from cultured myocytes exposed for 48 hours to 10-5, 10-6 and 10-7 M DXR were 27, 35, and 17 ng/ml respectively, compared with 14 in fluid from control (unexposed) myocytes and 0.47 in the culture medium alone. Thus, these data show that TT is realeased from DXR-damaged cardiac myocytes and that this alteration can be monitored by measurements of levels of TT.