In an effort to investigate the interaction of the adrenergic and enteric components of the autonomic nervous system, gut neuropeptide concentrations were examined following chemical sympathectomy. Adult male rats were treated with guanethidine (40 mg/kg i.p., 5 days/week for 5 weeks), which selectively destroys peripheral sympathetic neurons. Controls received equal volumes of saline vehicle. Tissues from fundic and pyloric stomach, duodenum, jejunum, jejuno-ileum, ileum, caecum and colon were extracted and concentrations of selected neuropeptides determined by radioimmunoassay. Dopamine-beta-hydroxylase (DBH) in peripheral nerve, measured as an index of degree of sympathectomy, was depleted 80-90%. One week after cessation of treatment, vasoactive intestinal peptide (VIP) was elevated in jejunum (52%), ileum (53%), caecum (41%) and colon (59%), as was neurotensin (NT) in caecum (117%) and colon (261%). Methionine-enkephalin (MET) was lowered in duodenum by 28%. With the exception of MET in duodenum and NT in caecum, these alterations normalized by 5 weeks post-treatment, although DBH remained depressed. Statistically non-significant increases in substance P content were observed in upper gut regions. An inhibitory sympathetic input to VIPergic and NTergic systems is postulated.