The sympathetic nervous system is an essential regulator of the cardiovascular system and interactions with target tissue regulate sympathetic neuronal properties. The heart produces nerve growth factor (NGF), which promotes sympathetic noradrenergic innervation of cardiac tissue and affects sympathetic synaptic strength. Neurotrophins, including NGF, are important modulators of synaptic plasticity and membrane electrical properties. Here we show that acute application of NGF causes a change in the repetitive firing pattern of cultured sympathetic neurons of the rat superior cervical ganglion. Neurons fire fewer action potentials in NGF, but with increased frequency, demonstrating an NGF-dependent change from a tonic to a phasic firing pattern. Additionally, NGF decreases the spike time variance, making spikes more tightly time locked to stimulus onset. NGF causes a decrease in the amplitude of both calcium-dependent and -independent potassium currents, and inhibition of calcium-dependent potassium currents using CdCl(2) reproduces some, but not all, of the firing properties induced by NGF. This study suggests that NGF release from cardiac tissue may act to modulate the repetitive firing properties of sympathetic neurons to tune their output to meet the physiological needs of the organism.