The most promising strategies for prevention of type 1 diabetes seem to be in the categories of immunomodulation (e.g., nondepleting anti-CD3, Diapep, linomide) and/or immunostimulation (e.g., QFA, BCG). We are currently undertaking a research program directed toward better understanding of immunostimulants to help maximize the likelihood of success of future human clinical trials for diabetes prevention. This program is focused on the key areas of optimization of vaccine dose and route of administration, development of surrogate immune markers, and elucidation of the mechanism of protection. The mechanism whereby QFA protects against diabetes currently is not known. The elucidation of the mechanism should help identify the optimal way in which to administer QFA to provide diabetes protection. It may also assist the development of even more potent immunostimulatory vaccines.