Betacellulin is a relatively new member of the epidermal growth factor peptide family, however, its function remains poorly defined. We investigated its physiological effects in rats implanted with pumps to deliver vehicle or recombinant rat betacellulin [46 microg/day] for 7 days. At kill, blood and gastrointestinal tissues were collected for determinations of betacellulin levels, proliferation (bromodeoxyuridine-BrdU incorporation) and growth. Plasma betacellulin levels were increased 8-fold compared to vehicle, whilst serum insulin, body weight and food intake were decreased by 32, 15 and 9%, respectively. Water intake, urine and faecal output and small intestinal weight were respectively increased by 36, 78, 47 and 24%. Ileal and proximal colonic crypt depths were increased by 25 and 51% although the BrdU labelling index was unaffected. Betacellulin stimulated gastrointestinal growth, the increased responsiveness of the terminal ileum and colon suggesting therapeutic potential in disease conditions in which ileal or colonic re-growth is desirable. Betacellulin further stimulated a diuresis suggesting an additional role in fluid homeostasis.