To determine if amniotic fluid or its constituent trophic factors influence fetal gastrointestinal tract development we developed models of fetal esophageal ligation to prevent swallowing of amniotic fluid and fetal esophageal cannulation with infusion of various substances to mimic fetal swallowing. A total of 43 fetuses was studied. Esophageal ligation resulted in a 32% reduction in gastric weight and a 40% reduction in serum gastrin level, compared to unoperated controls, whereas intestinal and liver weights were unchanged. Gastric acid concentration averaged 43.4 +/- 7.7 mumole/ml in control fetuses, but only 0.5 +/- 0.5 mumole/ml following esophageal ligation. Infusion of Ringer's lactate solution intragastrically did not prevent the changes in gut development seen after esophageal ligation. In contrast, infusion of bovine amniotic fluid resulted in relatively normal gut development, with a gastric acid concentration of 28.5 +/- 6.9 mumole/ml and liver and gastric weights and serum gastrin levels no different from control. Epidermal growth factor had a potent trophic effect on both somatic and gastrointestinal fetal growth and resulted in a mean gastric acid concentration of 35.2 +/- 6.6 mumole/ml. In contrast, pentagastrin, although restoring gastric weight to control values, had no effect on gastric acid secretion, with a mean of 0.1 +/- 0.1 mumole/ml. We conclude that fetal swallowing of amniotic fluid is essential in fetal gastrointestinal development, possibly via luminal trophic actions of peptides such as epidermal growth factor and gastrin.