1. Resveratrol, an active ingredient of red wine extracts, has been shown to exhibit neuroprotective effects in several experimental models. 2. The present study evaluated the neuroprotective effects of resveratrol against amyloid β(Aβ)-induced toxicity in cultured rat hippocampal cells and examined the role of the protein kinase C (PKC) pathway in this effect. 3. Pre-, co- and post-treatment with resveratrol significantly attenuated Aβ-induced cell death in a concentration-dependent manner, with a concentration of 25 μM being maximally effective. 4. Pretreatment (1 h) of hippocampal cells with phorbol-12-myristate-13-acetate, a PKC activator, at increasing concentrations (1-100 ng ml ), resulted in a dose-dependent reduction in Aβ-induced toxicity, whereas the inactive 4α-phorbol had no effect. 5. Pretreatment (30 min) of hippocampal cells with GF 109203X (1 μM), a general PKC inhibitor, significantly attenuated the neuroprotective effect of resveratrol against Aβ-induced cell death. 6. Treatment of hippocampal cells with resveratrol (20 μM) also induced the phosphorylation of various isoforms of PKC leading to activation. 7. Taken together, the present results indicate that PKC is involved in the neuroprotective action of resveratrol against Aβ-induced toxicity.