Various endothelial cells, with the exception of those from human microvasculatures, have been known to resist Shiga toxins (Stxs) in vitro. However, freshly prepared primary cultures of human endothelial cells from the umbilical vein and artery and the saphenous vein were shown to be killed by a very low dose of Stxs. This cytotoxicity of Stxs involves apoptosis, which seems to be caused by a mechanism distinct from the well-known action of Stxs to inhibit protein synthesis, since the blockade of protein synthesis by cycloheximide could not induce apoptosis or enhance the effect of Stxs. Passaged human endothelial cells have been found to be highly resistant to Stxs, which is consistent with previous reports, and not to show any evidence of apoptosis even when they are killed by a high dose of Stxs.