Keratinocyte growth factor (KGF) is a mitogen found throughout the gastrointestinal tract, but its role in gastrointestinal pathophysiology is unclear. The effect of recombinant KGF on gut growth and repair has been examined using a variety of in vivo models. Rats receiving total parenteral nutrition had co-infusions of KGF or control for 6 days. Changes in gut growth (wet weight and vincristine-induced metaphase arrest) were then assessed. The effects of KGF on gastric repair and acid secretion in rats were determined using an indomethacin (20 mg/kg)/restraint model and animals fitted with chronic gastric fistulae. KGF at 0.1, 1, and 3 mg/kg increased gut growth as assessed by wet weight throughout the gastrointestinal tract and increased vincristine-induced accumulation of metaphases in the stomach and small intestine but not in the colon. Plasma gastrin, peptide YY, enteroglucagon, and glucagon-like peptide-1 were all increased, whereas insulin was lowered by KGF (all P < 0.01). KGF was ineffective in reducing indomethacin-induced gastric damage but caused a reduction in basal acid secretion of about 35 and 50 per cent when administered at 0.2 or 5 mg/kg (P < 0.05). These studies support the idea that KGF is involved in the control of proliferation of the gastrointestinal tract. They do not provide evidence, however, for a role in the early reparative process invoked during short-term models of gastrointestinal injury.