Peripheral antigens can be captured by APC and cross-presented to naive CD8(+) T cells. Notably, cross-presentation of pancreatic antigen is not seen in neonatal mice, although presentation of antigen expressed by the kidney is still intact. In this report, we examined why pancreatic antigens are not cross-presented in neonatal mice. First, we established that antigen expression was not limiting, as neonatal islets expressed as much antigen per cell as adult islets, and vastly more than neonatal renal cells. Next, we analyzed the APC subsets present in the lymph node draining the neonatal pancreas. No obvious population was absent. Finally, we examined whether cross-presentation occurred during inflammation. This showed that inflammation caused by CTL attack of islet tissue facilitated cross-presentation of antigens in neonatal mice. These data indicate that constitutive cross-presentation of islet antigens is inactive during neonatal life, but that under inflammatory conditions this antigen presentation pathway becomes available.