The course of acute rejection of major histocompatibility complex (MHC)-incompatible isolated rat pancreatic islets transplanted under the kidney capsule was monitored functionally and histologically from day 1 to 10. The patterns observed were compared to those of vascularized whole-pancreas transplants with preserved and suppressed exocrine secretion. In addition the morphologic reactions after isogenic transplantation of islets or whole-pancreas transplants are described. The sequential patterns of acute rejection were found to be essentially identical in isolated islet and whole-pancreas allografts. This was also true for the process of I-A-like class II MHC antigen induction. Endocrine cell necrosis and reduced insulin content of beta cells were detected in isolated islets but not in whole-organ isografts. Thus ischemic damage may have occurred to be transplanted islets on days 1 and 2 because connections to the renal vasculature were not demonstrated before day 3. Islet cell loss was, however, functionally compensated by beta cell proliferation beginning on day 4. From the first day after transplantation, an altered spacial distribution of insulin- and glucagon-containing cells was present in islet isografts. This phenomenon was, however, not unique to islets, but also occurred in duct-ligated whole-organ isografts on days 6 to 10.