Understanding the influences of particle properties of antigen-adjuvant complexes on immunity is crucial in designing highly active adjuvants for new-generation of vaccines. This paper briefly revisits the current opinions on the size-dependent immunity of various adjuvant particles and then comprehensively discusses a few immunity-determining processes that are affected by the antigen-adjuvant particle properties. These include particle size, surface charge, surface hydrophilicity/lipophilicity, and antigen-adjuvant binding strength. Based on current understandings, we hypothesize that a maximum immune response occurs at a certain antigen-adjuvant particle size. This hypothesis clearly explains the paradoxical opinions on the size-dependent immunity and has also been supported by the data reported by several research groups. Finally, we further hypothesize that there is a similar relationship between any immune response and any measureable antigen-adjuvant particle property, and that there is a maximum immune response when all measureable antigen-adjuvant particle properties are optimized. We believe more attention should be paid to this issue when designing and developing effective adjuvants in future research. (C) 2012 Elsevier Inc. All rights reserved.