To determine the potential value of measuring adenylylcyclase activity as a pretransplant functional marker of pancreatic islet cell quality, a production rate of adenosine 3′:5′-monophosphate was measured with a fluorometric assay in rat islet cells before transplantation. Islets were stored for different periods of time (0 to 96 hours) and in different preservation solutions. The adenylylcyclase activities of islets stored in University of Wisconsin (UW) solution for 3 hours after isolation were significantly higher than those stored in Hank's balanced salt solution. Similarly, the adenylylcyclase activities of islets stored for more than 24 hours in UW solution decreased significantly with prolonged storage time. Preoperative adenylylcyclase activity was compared with post-transplant islet function in a rat model of diabetes. Transplant success was evaluated by measuring blood glucose level and body weight. Although all transplants were ultimately successful in this study, the rate at which they achieved euglycemia varied, and this is the property that correlated with pre-transplant basal or forskolin-stimulated adenylylcyclase activity. Additional studies showed that it was feasible to measure adenylylcyclase activity in human islet cells. We conclude that preoperative measurement of basal and stimulated adenylylcyclase activity may provide a useful clinical marker for assessing islet cell quality and differences in preservation media and may predict transplant success. Based on these data, additional studies evaluating the feasibility of using adenylylcyclase activity as a research and clinical marker of islet cell viability are warranted.