PAF has been implicated in the pathogenesis of acute gastric injury. When given peripherally, PAF induces severe gastric mucosal damage. PAF metabolizing enzymes are present in the brain but the central effects of PAF on the stomach are unknown. We have investigated in the rat the gastric secretion and gross mucosal integrity in response to intracerebroventricular (icv) PAF and compared it with that to icv TRH, a known central gastric secretagogue. Gastric acid output was markedly increased by TRH (171.6 +/- 26.3 mumol/h mean +/- SE) and by 20 micrograms/kg/h iv pentagastrin (107.6 +/- 23.6) when compared to controls receiving icv vehicle (20.2 +/- 7.5; p less than 0.01 for both). In contrast, acid output decreased after icv PAF (13.5 +/- 7.5). Furthermore, icv PAF markedly inhibited acid output stimulated by iv pentagastrin (45.1 +/- 7.03; p less than 0.05). Morphological studies showed acute gastric mucosal erosions after icv TRH and no damage was observed after icv PAF or vehicle. Thus, icv PAF reduces pentagastrin stimulated acid output and does not alter gastric mucosal integrity, whereas icv TRH stimulates acid secretion and induces gastric injury. The opposite effects of PAF and TRH suggests the existence of a gastric modulatory system at the central level.