WE examined the effects of nerve growth factor (NGF) on free radical neurotoxicity in striatal cell cultures. Following exposure to 30 μM Fe2+or 1 mM L-buthionine-[S, R]-sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, striatal neurons underwent cell body swelling and then widespread death over the next 2 4 h. The degeneration was prevented by addition of 100 μM trolox, an antioxidant. Addition of 100 ng/ml BDNF beginning 1 2 h before Fe2+or BSO potentiated necrosis of most striatal neurons after exposure to 1 μM Fe2+or 1 mM BSO. In contrast, treatment with 10 μng/ml NGF selectively potentiated the oxidative degeneration of striatal cholinergic neurons. The present findings provide additional evidence that NGF, like other neurotrophins, can potentiate oxidative neuronal cell necrosis.