The effects of epirubicin (EPIR), 5-fluorouracil (5-FU) and mitomycin C (MMC) on the vascular wall were examined histologically and pharmacologically. The popliteal arteries of rabbits were observed under a microscope one week after the injection of each anticancer drug. The histological change was not apparent. The rat thoracic aorta was removed and placed in the Krebs, solution. Helical strips were made, mounted in organ chambers and incubated with 10(5) mol/l (M) of each anticancer drug for 2 hours. After incubation, the relaxation response to acetylcholine (Ach) in endothelium-intact strips and that to sodium nitroprusside (SNP) in endothelium-denuded strips were evaluated. EPIR affected the relaxation response to Ach but not to SNP. 5-FU and MMC did not affect the relaxation responses to Ach and SNP. These results revealed that EPIR impairs the nitric oxide function at the level of endothelium. This effect of EPIR may be connected with arterial change following transarterial chemotherapy.