The effects of a single intravenous dose of guanidine hydrochloride were examined on the function of the lumbar dorsal-ventral root and triceps surae nerve-ventral root monosynaptic reflex (MSR) in unanesthetized acute spinal (C-1 sectioned) cats. Guanidine, in a dose of 25 mg/kg, consistently depressed the amplitude of the monosynaptic reflex response while a dose of 200 mg/kg always exerted a facilitatory action. Intermediate doses of 50 or 100 mg/kg produced variable actions on the amplitude of the monosynaptic reflex from one preparation to another. The differential effects of guanidine on the evoked monosynaptic reflex are postulated to represent the ability of the drug to enhance both excitatory and inhibitory transmission, the latter predominating at smaller doses and the former becoming apparent with an increasing dose of guanidine. The facilitatory and the depressant effects of guanidine on the function of spinal reflexes were slow to develop, suggesting an intracellular site of action. These results may have significance for an understanding of the possible efficacy of guanidine in motor neuron disease in man.