Adrenergic nerve terminals in several organs are selectively destroyed by 6-hydroxydopamine (6-OHDA) resulting in a chemical sympathectomy that is reversible. The acute and chronic effects of 6-OHDA on gastric mucosa and acid secretion were evaluated. Four dogs were given 6-OHDA (40 mg/kg, i.v.). Gastric biopsies were taken before treatment and biweekly thereafter and were analyzed by fluorescence microscopy (Hillarp-Falck). Degeneration of adrenergic nerve terminals in the mucosa was complete at 1 wk. Early regeneration was noted at 3 wk and appeared to be complete at 9 wk. In another group of 7 dogs with a gastric fistula, dose-response curves to pentagastrin (PPG, 0-5 .mu.g/kg per h) were determined. The 6-OHDA (40 mg/kg) was given to these dogs and secretory studies were repeated weekly thereafter for 8 wk. After 6-OHDA administrations, acid secretion increased in response to submaximal doses of PPG; maximal secretion was unchanged. The peak increase occurred the 2nd wk; thereafter secretion gradually returned to control values. Chemical sympathectomy (6-OHDA) increases gastric acid secretion in response to submaximal PPG stimulation. This increase correlates well with the 6-OHDA-induced degeneration of adrenergic terminals in the mucosa. The adrenergic innervation of the stomach apparently has an inhibitory effect on the control of acid secretion in the dog.