Akt plays an important role in various physiological and pathophysiological pathways. Binding of 3``-OH phosphorylated phosphoinositides to the PH domain results in translocation of Akt to the plasma membrane where Akt is activated by phosphorylation by upstream kinases. In addition to this protein phosphorylation mediated regulation of Akt activity, other regulatory mechanisms for Akt have been sought. Here I demonstrated that Akt interacts with itself forming dimers which affected the activity and subcellular localization of the kinase. I investigated the dimerization domain of Akt through coimmunoprecipitaton of serial deletion mutants of Akt with wild type Akt, and determined that the dimerization domain lies within amino acids 129-138 in the linker region. In COS cells, the activity of an Akt deletion mutant, lacking the dimerization domain and PH domain, was dramatically decreased and this decreased activity was highly correlated with the lack of Thr308 phosphorylation. These data implicate that the self-association of Akt plays an important role in the regulation of Akt activity and that the linker region is a critical mediator of structural organization of Akt.