Orthodromic, preganglionic conditioning stimulation can consistently induce long-term enhancement (LTE) (greater than 3 h) of the muscarinically mediated slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential. This was shown for superior cervical ganglia of rabbit and rat. Effective conditioning stimuli are in a physiologically observed range (3/s for 7 min, 5/s for 4 min, 10/s for 2 min, 20/s for 1 min). LTE was producible both homosynaptically and heterosynaptically. LTE can thus be associative, with conditioning synaptic input in one line inducing long-term changes in postsynaptic responses to another (heterosynaptic) input. The dopamine antagonist butaclamol depressed LTE, particularly that following the initial postconditioning period of 30 min. Adrenergic antagonists had no effect. This pharmacological evidence, coupled with the heterosynaptic induction of LTE, supports the view that neurally induced LTE may be at least partly mediated by endogenous dopamine. Another non-cholinergic but non-adrenergic transmitter (possibly a peptide) might contribute to the LTE seen in the initial 30 min postconditioning. The present, orthodromically induced LTE is clearly different from the long-term potentiation widely studied in hippocampus, etc., in the modes of induction and synaptic mediation.