An amyloid-binding dye Congo red has been reported to prevent the neurotoxic effect of Alzheimer's amyloid β protein (Aβ). In the present study, we investigated the effect of Congo red in cultured rat cortical astrocytes. Aβ (1 nM-10 μM) did not cause cell death, but potently inhibited the cellular redox activity as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Congo red (0.2-20 μM), when added together with or prior to Aβ, significantly blocked Aβ-induced inhibition of redox activity. Furthermore, when Congo red was added after treatment with Aβ, the inhibited redox activity was restored to normal, indicating that Congo red can reverse Aβ-induced cellular stress. The reversing effect of Congo red cannot be explained by the inhibition of Aβ fibril formation and suggests a novel aspect of the interaction of Congo red with Aβ.