Validation of catheter-based intravascular ultrasound imaging has been based on comparisons with histology and digital angiography, each of which may have limitations in the assessment of arterial size and morphology. External, high-frequency ultrasound can accurately determine vessel dimensions and morphology and because, like ultravascular ultrasound, it also provides cross-sectional arterial ultrasound images, it may be a more appropriate technique for the in vivo comparison of arterial dimensions and morphology determined by intravascular ultrasound. Thus, intravascular ultrasound, external 2-dimensional ultrasound, Doppler color-flow imaging and digital angiography were compared for assessment of arterial dimensions and wall morphology at 29 femoral artery sites in 15 patients. Intravascular ultrasound and the other 3 imaging modalities correlated well in determination of lumen diameter (2-dimensional, r = 0.98, standard error of the estimate [SEE] = 0.14; Doppler color flow, r = 0.91, SEE = 1.11; angiography, r = 0.95, SEE = 0.91) and cross-sectional area (2-dimensional, r = 0.97, SEE = 0.04; Doppler color flow, r = 0.92, SEE = 0.14; angiography, r = 0.96, SEE = 0.08). However, lumen size measured by Doppler color flow was consistently smaller than that measured by the other 3 imaging modalities. Intravascular ultrasound detected arterial plaque at 15 sites, 5 of which were hypoechoic (soft) and 10 hyperechoic with distal shadowing (hard). Plaque was identified at 12 of 15 sites by Z-dimensional imaging (p = 0.30 vs intravascular ultrasound), but at only 6 of 15 sites by angiography (p = 0.003 vs intravascular ultrasound), only 1 of which was thought to be calcified plaque.(ABSTRACT TRUNCATED AT 250 WORDS)