The role of monoamines in the transsynaptic reduction of neuronal activity produced by delta 9-tetrahydrocannabinol (delta 9-THC) in the septal-hippocampal cholinergic pathway has been investigated. Serotonergic afferents were chemically lesioned by unilateral infusion of 5,7-dihydroxytryptamine. Noradrenergic and dopaminergic inputs were selectively deleted by unilateral infusion of 6-hydroxydopamine into appropriate anatomic sites. Although removal of serotonergic and noradrenergic input did not alter hippocampal choline uptake relative to the contralateral control side, dopaminergic input reduction produced a significant elevation. After administration of delta 9-THC (20 mg/kg), reduction of choline uptake into lesioned hippocampi was not significantly different from that for the controls. These results indicate that monoaminergic afferents do not play a major role in the effect of delta 9-THC on cholinergic activity in the rat hippocampus.