S-Adenosyl-l-methionine has been shown to cause Parkinson's disease-like effects that include hypokinesia, tremor, rigidity, and abnormal posture. S-Adenosyl-l-methionine is the rate-limiting endogenous methyl donor. Its biochemical role, which includes the metabolism of dopamine and the synthesis of acetylcholine, also resembles the changes that occur in Parkinson's disease. Therefore, S-adenosyl-l-methionine may play a role in Parkinson's disease-like motor impairments. In this study we manipulated the levels of S-adenosyl-l-methionine in the brain of rats and quantified the changes in hypokinetic type motor activity that seems to occur also in Parkinsonism. Male Sprague—Dawley rats were anesthetized with chloral hydrate (400 mg/kg/rat), cannulated, injected into the lateral ventricle with S-adenosyl-l-methionine or saline, and their motor activity was measured in a Digiscan Animal Activity Monitor. Other behaviors were also observed. S-Adenosyl-l-methionine caused hypokinesia, tremor, rigidity, and abnormal posture in rats. Motor activity was significantly decreased within 2 min postinjection. The hypokinesia was maximal at 60 min, at which time a 65, 75, and 90% decrease for total distance, number of movements, and the ratio of total distance to the number of movements occurred, respectively. The hypokinetic effect of S-adenosyl-l-methionine was dose dependent. A 65.0 and 51.3% decrease in total distance and number of movements, respectively, were observed following 9.38 × 10−9 mol. The 5.0 × 10−8 mol caused a reduction of 73.42 and 57.66% and 4.0 × 10−7 mol/rat caused a 94.9 and 78.43% decrease, respectively. A dose of 200 mg/kg l-dopa, the main therapeutic agent for Parkinson disease, blocked the hypokinetic effects of 5.0 × 10−8 mol S-adenosyl-l-methionine, but d-dopa, the inactive analog, showed no effect. S-Adenosyl-l-methionine is an important endogenous substance used in the metabolism of catecholamines via trans-methylation. In excess quantities, it may deplete dopamine, the major neurotransmitter that is depleted in Parkinson's disease. Therefore, these findings suggest that S-adenosyl-l-methionine-induced hypokinesia, and its associated symptomatology, may serve as a model for the study of Parkinsonism and it may in fact be involved in the etiology of the disease.