Early diagnosis of rejection in pancreas-allograft transplantation remains a clinical challenge. The aim of this study was to assess the ability of antirejection therapy to reverse rejection when the diagnosis was based on either fine-needle aspiration biopsy (FNAB) or urinary amylase (UA). Sixteen dogs received a total-pancreas allograft with exocrine drainage into the bladder. Initially, a deliberately low dose of cyclosporin was given. Monitoring included percutaneous FNAB with ultrasound guidance and fasting spot measurements of UA. The diagnosis of rejection was made in alternate dogs when UA fell to less than 5000 IU/L (group A) or when the total corrected increment (TCI) of aspirated infiltrating cells was greater than 2.6 (group B). Antirejection therapy consisted of 10 mg.kg-1.day-1 i.v. methylprednisolone for 5 days and an increased dose of cyclosporin (25 mg.kg-1.day-1). The median allograft survival was 9 days (range 8-19) in group A and 32 days (range 10-63) in group B (P = .01). A fall in UA permitted the successful reversal of rejection in only one of six grafts, whereas five of seven grafts were successfully treated when rejection diagnosis was based on FNAB. In conclusion, early diagnosis of rejection was achieved by FNAB, improving the ability of antirejection therapy to reverse pancreas-allograft rejection and prolong survival.