This study determined if the vagus nerve can regenerate and/or reinnervate the gastric parietal cell mass after parietal cell vagotomy (PCV) and examines tests for assessing vagus nerve regeneration in rats. Microscopic dissection of the neurovascular bundle allowed the vagus nerve to be divided at the gastric body with preservation of the antropyloric nerve and gastric vasculature. Gastric secretory tests were performed under basal and stimulated conditions using secretagogues and insulin hypoglycemia. The candidate hormone, pancreatic polypeptide, was measured in plasma following a mixed meal, insulin hypoglycemia and i.v. secretin. Rats were killed weekly for 9 weeks and the vagal nerve distribution examined by both light and electron microscopy. Stimulated gastric acid output fell from 164 to 26 mumol/h immediately after operation (P less than 0.001). One week following PCV, the nerves were swollen with fibroblast infiltration and collagen around axon groups showed degeneration. By the third week after PCV, the axons were more densely packed with neurofilaments and acid output had increased to 183 mumol/h. In the fourth and fifth weeks, the enlarged Schwann cell processes had more axons and acid output rose to 262 mumol/h. By the seventh week, both large and small axons were identified and the acid output was 93% higher than the preoperative level (P less than 0.001). PCV and antrectomy also was followed by reinnervation of the gastric mucosa. Pancreatic polypeptide concentration in plasma was virtually unchanged following ingestion of food, insulin hypoglycemia or secretin. In rats, following PCV, gastric secretory tests and electron microscopy seem to be the most reliable methods of assessing vagus nerve regeneration.