1. Tritiated agmatine has been used by others in ion flux methods to measure nicotinic receptor function in neurones. However, as shown here, agmatine blocks nicotinic receptor function in both the chick retina and the rat superior cervical ganglion at high concentrations. 2. In intact chick retina, agmatine 1 mM decreases dimethylphenylpiperazinium (DMPP)-induced depolarizations measured in the optic nerve by approximately 70%, while having little effect on responses induced by glutamate analogues. DMPP dose-response curves are reduced in a manner consistent with a non-competitive effect of agmatine, and agmatine at 1 mM does not prevent binding of 125I-labelled neuronal bungarotoxin, a snake venom neurotoxin that competitively binds and blocks functional nicotinic receptors in chick retinal homogenates. 3. Agmatine (10 mM) substantially blocks both DMPP-induced depolarizations of rat superior cervical ganglion and synaptic transmission through the ganglion. Others have established that [3H]-agmatine will pass through nicotinic receptor channels in the rat ganglion. These data suggest that agmatine acts both as a cation and as a weak channel blocker at neuronal nicotinic receptors.