Database survey in this study revealed that about one-third of the protein. structures deposited in the Protein Data Bank (PDB) Contain arginine arginine (Arg-Arg) pairing with a carbon center dot center dot center dot carbon (CZ center dot center dot center dot CZ). interaction distance less than 5 A. All the Arg-Arg pairings were found to bury in a polar environment: composed of acidic residues, water molecules, and strong polarizable or negatively charged moieties from binding site or bound ligand. Most of the Arg-Arg pairings are solvent exposed and 68.3% Arg-Arg pairings are Stabilized by acidic residues, forming Arg-Arg-Asp/Glu clusters. Density functional theory (DFT) was: then employed to study the effect of environment on the poring structures It Was revealed that Arg-Arg pairings become thermodynamically stable (about -1 kcal/mol) as the dielectric constant increases to 46.8 (DMSO), in good agreement with the results of the PDB survey. DFT calculations also demonstrated that perpendicular Arg-Arg pairing structures are favorable in low dielectric constant environment, while in high dielectric constant environment parallel Structures are favorable: Additionally, the acidic residues can stabilize the Arg-Arg pairing structures to a large degree:, Energy decomposition analysis of Arg-Arg pairings and Arg-Arg-Asp/Glu clusters showed that both solvation and electrostatic energies contribute significantly to their stability. The results, reported herein should be very helpful for understanding Arg-Arg pairing and its application in drug design.