The effect of S-adenosyl-L-methionine (SAM) on neuronal degeneration induced by transient forebrain ischemia was studied in rats. Bilateral occlusion of the common carotid arteries for 30 min in a 4-vessel occlusion model caused degeneration of CA1 neurons of the hippocampus. When SAM-HCl or SAM sulphate tosylate (SAM-ST, 100 mg/kg as the free form of SAM, i.p.) was administered just after recirculation and every hour for 5 h after recirculation, the degeneration and loss of pyramidal cells were prevented. However, adenosine, a metabolite of SAM, and glycerol, which has the same osmotic pressure as the solution of SAM-ST, did not show any effects on the neuronal damage. The results showed that SAM has a beneficial effect on neuronal damage induced by ischemia.