In vivo identification of plaque composition may allow the detection of vulnerable plaques before rupture. However, the clinical relevance of multidetector computed tomography (MDCT) in characterizing coronary plaques is currently a subject of debate. We compared 64-slice MDCT with virtual histology to investigate the potential role of 64-slice MDCT in the differentiation of composition of noncalcified coronary plaques. Fifty-nine consecutive patients (stable/unstable angina 34/21) were enrolled. Mean computed tomographic (CT) density (Hounsfield units) of noncalcified coronary plaques (n = 80) was compared with a relative volume of each plaque component (fibrous, fibrofatty, calcium, and necrotic core) analyzed by virtual histology. Mean heart rate during MDCT was 58 +/- 9 beats/min. There was a negative correlation between mean CT density and the necrotic core (r = -0.539, p <0.001) and a positive correlation between mean CT density and the fibrotic tissue component (r = 0.571, p <0.001). Mean CT density of the plaques with a <10% necrotic core was significantly higher than that of a >or=10% necrotic core (93.1 +/- 37.5 vs 41.3 +/- 26.4 HU, p <0.001). However, overlapping of mean CT densities between plaques with a <10% necrotic core and those with a >or=10% necrotic core was found. In conclusion, mean CT density of noncalcified coronary plaques measured by 64-slice MDCT may depend on the relative volumes of the necrotic core and fibrotic component. Sixty-four-slice MDCT may have the potential for determining composition of noncalcified coronary plaques, which needs further studies for clinical application.