The reactivity of sinusoids in hepatocellular carcinoma (HCC), focal nodular hyperplasia, and nonneoplastic liver tissue with various endothelial markers was investigated to detect any differences that might be of diagnostic relevance. The lectin UEA-1 antibody BMA 120, and antibodies against von Willebrand's factor, CD31, and CD34 were used. KP1 was employed to detect Kupffer cells. In the normal liver there was only focal staining of sinusoidal endothelium in the vicinity of the portal tracts with all of the endothelial markers applied. In the cirrhotic liver a slightly greater number of sinusoids (mainly in the vicinity of the fibrous septa) stained with UEA-1 and, although to a lesser extent, with anti-von Willebrand's factor and anti-CD31. A slight increase in staining for CD34 was seen in only 1 of the 11 specimens of cirrhotic liver. In focal nodular hyperplasia, there was increased staining of sinusoids with all of the markers investigated; staining was confined mainly to the periphery of the nodules. HCC exhibited the most obvious differences in numbers of stained sinusoids and staining intensity in comparison with both normal and cirrhotic liver. UEA-1 and anti-CD34 stained large numbers of sinusoids in virtually all of the HCC investigated; UEA-1 stained a slightly greater number of sinusoids and did so with slightly greater intensity. BMA 120 and the antibodies against von Willebrand's factor and CD31 stained a smaller number of sinusoids and did so with lower intensity; they failed to stain sinusoids in some of the tumors. Because staining of the sinusoids in cirrhotic liver was minimal with anti-CD34, this antibody proved to be the best of all the markers investigated for distinguishing highly differentiated HCC from nonneoplastic liver tissue. It seems possible that the increase in immunoreactivity of sinusoids in HCC with anti-CD, unlike that with Uea-1, anti-von Willebrand's factor, and anti-CD31, is not an expression of capillarization, but rather of angiogenesis.