The angiogenic process plays an important role in tumour growth and metastasis during hepatocarcinogenesis, but it is still uncertain when the process begins during tumour formation. Forty-two small hepatocellular carcinomas (HCC) that measured either less than or equal to 2 cm in diameter were studied by comparing the histologic findings with the angiographic findings, and with immunohistochemical expression of endothelial marker QB-end/10 (QB), a new monoclonal antibody raised against CD34, in the sinusoidal wall. Twenty (91%) of 22 moderately or poorly differentiated HCC revealed a positive reaction for QB, while only eight (40%) of 20 well differentiated HCC demonstrated a positive reaction (P < 0.01). In the tumours showing a 'nodule in nodule' appearance, the less differentiated areas were more reactive for QB. Twenty-three (82%) of 28 QB positive tumours were hypervascular, while only three of 14 (21%) QB negative tumours were hypervascular (P < 0.01) by angiography. All six of the poorly differentiated and 13 (81%) of the 16 moderately differentiated tumours were hypervascular, while only seven (35%) of 20 well differentiated HCC were hypervascular (P < 0.01). These results indicate that as the tumour becomes less differentiated, the QB positive areas become wider and angiography demonstrates hypervascularity. We therefore speculate that the HCC sinusoids acquire the characteristics of capillary and precapillary blood vessels during de-differentiation from well to moderate, and thus the tumour begins to reveal hypervascularity on angiography. The above process may be correlated with the stepwise progression of HCC.