Sympathetic ganglia are the major contributors to the stress-elicited rise in circulating norepinephrine, enkephalins, and neuropeptide Y. Here we examined the effect of immobilization stress and treatment with ACTH and glucocorticoids on messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), preproneuropeptide Y (pre-NPY), and proenkephalin in rat superior cervical ganglia (SCG) and in stellate ganglia. Our results show a severalfold increase in the relative abundance of TH and NPY mRNAs in response to a single immobilization. Repeated stress elevated expression of all the genes studied and increased TH immunoreactivity in both ganglia. The effect of stress was more pronounced in SCG. Prolonged cortisol administration failed to alter the mRNA levels of TH, DBH, and NPY in control animals but attenuated the response to stress. In contrast, TH and DBH mRNA levels in the SCG, but not in adrenal medulla, were elevated by ACTH administration, similar to the levels attained after immobilization. The results revealed that the regulation of gene expression in response to immobilization stress in sympathetic neurons differs from the regulation in adrenal medulla. The study implicates hormonal involvement in the stress-induced changes in TH, DBH, NPY, and proenkephalin gene expression in sympathetic ganglia.