insulin in the blood were then monitored over the next hour. The results (see Figure 4.2) show that there is a significant insulin release (interpreted as a surrogate for islet destruction) in the untreated group. This insulin release is greatly reduced when complement activation is inhibited [50]. All of these data taken together strongly support the contention that adult pig islets exposed to human or primate blood suffer significant immediate posttransplant damage. This conclusion is supported by the studies of Contreras and colleagues [20, 21] using rhesus monkey serum and by Rayat et al. [64] using human serum, both of whom reported similar porcine islet cell destruction. In contrast, Mirenda and colleagues [51, 52] failed to achieveisletcelllysiswhenexposingpigisletstohuman serum that was diluted 50%. This suggests that destruction of porcine islets is highly concentration dependent (though of what is not known). It is also unclear as to what percentage of islets is rendered nonfunctional by this humorally mediated damage. Furthermore, if pig islets are damaged by humoral factors in primate and human serum why do they survive when transplanted into nude diabetic mice [26]? There are at least three possible explanations for this: (1) nude mice have inadequate complement activity [71], (2) antibody critical to the destruction of the islets is T-cell dependent [82], or (3) the site of transplantation (in this case, under the kidney capsule) confers some protection to the pig islets. In support of this last hypothesis, Brandhorst and colleagues [12] demonstrated that pig islet transplanted under the kidney capsule of nude diabetic rats could maintain reasonable carbohydrate control while