The nicotinic cholinergic transmission causing generation of the fast EPSP in bullfrog sympathetic ganglia is modulated by the action of transmitters or hormones other than ACh. In general, a synaptic transmission appears to be modulated in a variety of ways by the action of many kinds of transmitters or hormones in the vertebrate neural system. There are at least four different types of modulatory actions of these endogenous substances on a synaptic transmission; namely, 1) modulation of the amount of the transmitter released from presynaptic neurones, 2) modulation of the sensitivity of the receptors of postsynaptic neurones, 3) modulation of the resting membrane potential or conductance of postsynaptic neurones, and 4) modulation of the configuration of the action potential of postsynaptic neurones. In the present review, the experimental evidence supporting the modulatory actions of endogenous substances on the receptor sensitivity and the action potential of postsynaptic neurones was reviewed. The mechanisms underlying these two types of modulatory actions were also briefly discussed.