Inactivation of gastrin was studied (a) in vitro by incubation with a high-speed supernatant fraction of rat small bowel mucosa and (b) in vivo by perfusing gastrin through the small bowel vascular bed in anaesthetized dogs. In both types of experiment there was a highly significant loss in the bioactivity of gastrin, but no significant change in its immunoreactivity. This showed that gastrin was inactivated by a subtle chemical change which rendered the molecule biologically inactive, yet left its immunoreactivity unimpaired.