Although vagotomy reduces acid secretion in vivo, the effects of vagotomy at the level of the parietal cell are not known. In the present study we examined the in vitro secretory characteristics of parietal cells in rabbits 8 weeks following vagotomy compared to unoperated and sham-operated controls. Acid secretion was assessed by the uptake of [14C]aminopyrine (AP) in isolated gastric glands. Also, gastric fundus histology, mucosal thickness, parietal cell density, and gastric gland somatostatin content were examined. Basal AP uptake was decreased following vagotomy (8 +/- 0.4 pmole/mg dry wt) compared to controls (21 +/- 2) (P less than 0.001). Increase in AP uptake by the cholinergic agonist carbachol was unaffected after vagotomy (P greater than 0.5) suggesting intact muscarinic receptors and calcium second messenger system. Increase in AP uptake was significantly reduced following vagotomy by the cyclic AMP-mediated agonist histamine (P less than 0.05) and the cyclic AMP mimetic 8-bromo cyclic AMP (P less than 0.001) suggesting an alteration in the ability of the parietal cell to utilize cAMP following vagotomy. There were no discernible differences in histology, mucosal thickness, or parietal cell number in vagotomized animals compared to controls (P greater than 0.5). There was a significant increase in gastric gland somatostatin content following vagotomy (37 +/- 10 fmole/mg dry wt) compared to control (14 +/- 1.5) (P = 0.025). These results suggest that there is a decrease in the capacity of parietal cells to secrete acid following vagotomy. In addition, the decrease in cAMP utilization following vagotomy suggests that the cAMP second messenger system is dependent, at least in part, on an intact vagus nerve.