Intestinal secretion was evoked in periarterially denervated jejunal segments of anesthetized rats and cats by exposing the intestines to the heat stable (ST) toxins from a strain of Escherichia coli producing both STa and STb toxins. The secretion was significantly inhibited and to about the same relative extent by the addition of each one of the three following drugs: hexamethonium (i.v., rats), lidocaine (applied on the serosal surface, rats) and tetrodotoxin (intra-arterial, cats). Atropine inhibited fluid secretion in some experiments. It is proposed that a nervous mechanism is mediating part of the secretory response to Escherichia coli heat stable toxins, since three different drugs, which influence nervous activity in different ways, significantly diminished the secretory response. A model for the secretory nervous reflex(es) within the enteric nervous system is proposed; Escherichia coli heat stable toxins activate a "receptor cell" in the epithelium, which then stimulates surrounding dendritic nerve endings via the release of unknown substance(s). A nicotinic receptor is involved but further characteristics of the nervous reflex(es) remain to be elucidated.