Urinary levels of immunoreactive insulin (IRI) were measured in 18 pigs subjected to pancreatic allograft transplantation with exocrine drainage into the urinary tract. Fifteen pigs were given no immuosuppressive therapy while 3 pigs received cyclosporine and prednisolone. The onset of rejection was defined as an increase in the serum levels of anionic trypsin (irAT). Urinary levels of IRI were compared between normo- and hyperglycemic pigs representing slow and fast rejectors. It was possible to measure insulin in the urine from all these pigs with a pancreatic allograft, and the urinary IRI levels increased after an intravenous injection of secretion and cholecystokinin. We found that urinary IRI response to secretin and cholecystokinin declined during rejection. By contrast, baseline, unstimulated urinary IRI levels did not correlate with rejection. No advantage was seen in the determination of urinary IRI when compared to determination of urinary irAT. In pigs not treated with immunosuppressants (with irreversible rejection), stimulated urinary levels of IRI and irAT were highly useful as graft-function indicators, whereas in immunosuppressed pigs (with reversible rejection episodes) they seemed to complement each other.