Although associated primarily with the cardiovascular system, atrial natriuretic factor (ANF) has been found to increase the magnitude of duodenal contractions and may play a role in salt and water absorption across gastrointestinal epithelium. Because secretory diarrhea and increased peristalsis are commonly associated with conditions related to hypergastrinemia, we examined an animal model of hypergastrinemia (fundusectomy) to evaluate a possible role for ANF. Sprague-Dawley rats underwent either fundusectomy or sham operation. Circulating levels of gastrin (1085 +/- 105 vs 59 +/- 5 pg/ml), ANF (209 +/- 50 vs 59 +/- 10 pg/ml), and pro-ANF 1-98 (786 +/- 80 vs 599 +/- 49 pg/ml) were elevated significantly 3 months after fundusectomy versus control animals. The increased levels of ANF and pro-ANF 1-98 correlated with the increased gastrin levels (p less than 0.05). Tissue content of ANF and pro-ANF 1-98 were determined at sequential sites in the stomach and small intestine. In normal rats ANF concentrations were greatest in the small intestine; pro-ANF 1-98 content was similar in all tissues except ileum (increased). In rats that underwent fundusectomy, ANF and pro-ANF 1-98 were markedly increased in duodenum compared with all other tissues. Only duodenum showed a difference in peptide levels between normal rats and rats that underwent fundusectomy, (ANF, 1.5 +/- 0.5 vs 16.7 +/- 2.3 ng/gm; pro-ANF 1-98, 0.6 +/- 0.3 vs 51.2 +/- 36.1 ng/gm). Circulating ANF and pro-ANF 1-98 are increased in rats that have undergone fundusectomy. Our results suggest that duodenum may be the source of these increased levels.