The neuropathological hallmarks of Alzheimer's disease (AD) are senile plaques, cerebrovascular β-amyloidosis, neurofibrillary tangles, and selective neuronal loss. β-Amyloid (Aβ) has been shown to cause vascular damage mediated by generation of reactive oxygen species and this damage is considered an early event in the development of AD. In this study, we determined the effect of pycnogenol, a potent antioxidant phytochemical, on Aβ-induced cellular injury. Pulmonary artery endothelial cells (PAEC) were exposed to Aβ for 24 h. Cell injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by determining the release of intracellular lactase dehydrogenase (LDH). Lipid peroxidation products of PAEC were determined by measuring thiobarbitric acid-reactive substances (TBARS). Exposure of PAEC to Aβ resulted in a decrease in cell viability, an increase of LDH release indicating membrane damage, and an elevated level of TBARS. Preincubation of PAEC with pycnogenol significantly minimized these changes. This study demonstrated that pycnogenol can protect vascular endothelial cells from Aβ-induced injury. The data suggest that pycnogenol may be useful for the prevension and/or treatment of vascular or neurodegenerative diseases associated with Aβ toxicity.