We quantified microvessel morphology and vascular endothelial growth factor (VEGF) expression in human colonic carcinoma with or without metastasis. The cancerous growth and the noncancerous section of surgical specimens from 36 patients with colorectal carcinoma (14 without metastasis and 22 with metastasis) were studied. Tissue slices immunostained with CD34 were processed for microvessel counts (per mm(2)), the mean diameter of microvessels (microm), and the mean spatial direction of microvessels (degree), defined by the angle between the longitudinal axis of microvessels and the direction perpendicular to the surface of the mucosa. Tissue slices immunostained with anti-VEGF antibody were processed for total epithelial cell counts (per mm(2)), VEGF-positive cell counts (per mm(2)), and VEGF-positive ratio (%). Carcinoma without metastasis had significantly larger microvessel counts (213 +/- 77, p < 0.01), larger microvessel diameter (7.99 +/- 1.77, p < 0.05), and larger spatial direction (47.2 +/- 8.3, p < 0.01) than normal tissue (144 +/- 49 for microvessel counts; 7.03 +/- 0.90 for microvessel diameter; 39.5 +/- 6.6 for spatial direction). Compared with carcinoma without metastasis, carcinoma with metastasis had a significantly larger microvessel diameter (9.75 +/- 2.65, p < 0.03) and lower microvessel counts (180 +/- 92, p = 0.51). Carcinoma without metastasis had a significantly larger VEGF-positive cell count (1276 +/- 805, p < 0.05) and larger VEGF-positive ratio (53.6 +/- 39.3, p < 0.05) than normal tissue (571 +/- 553 for VEGF-positive cell counts; 24.6 +/- 23.2 for VEGF-positive ratio). Carcinoma with metastasis had a significantly lower total cell count (1443 +/- 237, p < 0.001) and lower VEGF-positive cell count (716 +/- 463, p < 0.05) than carcinoma without metastasis. With tumor progression, microvessel diameter significantly increased and microvessel counts decreased, which can be in part explained by VEGF expression. The microvessel diameter seems to be the dominant parameter responsible for cancer cell intravasation as the first step of metastasis.