The effects of increased synaptic stimulation of sympathetic neurons on the tyrosine hydroxylase activity of these cells were studied. Seventy-two hours after unilateral stimulation of the preganglionic cervical sympathetic trunk at 10 Hz for 30 min tyrosine hydroxylase activity was 32% higher in stimulated than in control superior cervical ganglia. Stimulation at 10 Hz for only 10 min increased enzyme activity by 25% when measured 72 h later, while stimulation for 60 min increased activity by 73%. No further change in enzyme activity was found after 90 min of stimulation although electrophysiological recordings from the ganglion demonstrated that synaptic transmission was maintained throughout the period of stimulation. Ganglionic neurons also follow high frequency trains of stimuli when they are interrupted by silent periods. Stimulation with 40 Hz trains (250 msec on/500 msec off) for 30 min and 90 min produced a 50% and a 92% increase in tyrosine hydroxylase activity, respectively. Stimulation of ganglia with the same number of pulses administered either continuously or in trains produced the same size increase in enzyme activity. The relationship between preganglionic nerve activity and tyrosine hydroxylase activity may represent an adaption of sympathetic neurons to situations requiring increased transmitter release.