To extend intravascular ultrasound(IVUS) conventional analysis, we have developed a novel method used to automatically assess artery and lumen dimensions using a snake curve method based upon B-splines. To validate this system, fresh postmortem human coronary artery segments(n=9) of lengths ranging from 10-22 mm were analyzed by manual, automated, and histomorphometric methods(histo). IVUS analysis was performed using 3.9F,30 MHz IVUS catheter(CVIS) with motorized pullback (.5mm/sec). Manual measurements were made of external elastic membrane(EEM), lumen(LUM), plaque and media complex(P+M=EEM-LUM), and %area stenosis(%STEN=P+M/EEM*100). Images obtained off-line every 2mm were matched to site-specific cross sections and correlated to automated and histo analyses(n=79). Intra- and interobserver manual analyses comparing measurement parameters demonstrated a correlation coefficient (r=0.89-0.98;p<0.01 and 0.87-0.98;p<0.01, respectively). The automated method generated contours that were manually verified and required correction in 5% of the segments. Area analyses by the automated system demonstrated a strong agreement to both manual analysis(r=0.91-0.98; p<0.001) and histo(r=0.78-0.96;p<0.001) with a low mean between-method difference(Delta) of -.04+/-0.43 and -.04+/-0.9, respectively. Volumetric analysis also demonstrated strong agreement to manual and histo(r=0.97-0.99 and r=0.96-0.98)with mean delta of -.71+/-4.91 and -.71+/-4.83, respectively. In particular, the plaque volume determined by the automated method was highly correlated(r=.97) with the volume estimate by histo with mean Delta of 5.45+/-16.13. This new automated method permits the reliable quantitative assessment of coronary artery atherosclerosis and should prove useful in future clinical trials.