This study investigated the accuracy and reproducibility of a computer-aided method for quantification of intravascular ultrasound. The computer analysis system was developed on an IBM compatible PC/AT equipped with a framegrabber. The quantitative assessment of lumen area, lesion area and percent area obstruction was performed by tracing the boundaries of the free lumen and original lumen. Accuracy of the analysis system was tested in a phantom study. Echographic measurements of lumen and lesion area derived from 16 arterial specimens were compared with data obtained by histology. The differences in lesion area measurements between histology and ultrasound were minimal (mean +/- SD: -0.27 +/- 1.79 mm2, p greater than 0.05). Lumen area measurements from histology were significantly smaller than those with ultrasound due to mechanical deformation of histologic specimens (-5.38 +/- 5.09 mm2, p less than 0.05). For comparison with angiography, 18 ultrasound cross-sections were obtained in vivo from 8 healthy peripheral arteries. Luminal areas obtained by angiography were similar to those by ultrasound (-0.52 +/- 5.15 mm2, p greater than 0.05). Finally, intra- and interobserver variability of our quantitative method was evaluated in measurements of 100 in vivo ultrasound images. The results showed that variations in lumen area measurements were low (5%) whereas variations in lesion area and percent area obstruction were relatively high (13%, 10%, respectively). Results of this study indicate that our quantitative method provides accurate and reproducible measurements of lumen and lesion area. Thus, intravascular ultrasound can be used for clinical investigation, including assessment of vascular stenosis and evaluation of therapeutic intervention.