The three isoenzymes of NO synthase (NOS) catalyze the conversion of L-arginine to nitric oxide (NO) and citrulline: the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS), and the induced isoform - iNOS. There is considerable experimental evidence that the excessive NO production following induction of iNOS plays an important role in the pathology of a large number of inflammatory diseases. Recent studies revealed that GW274150, a potent and highly selective iNOS inhibitor, displays analgesic effects in rat models of inflammatory and neuropathic pain. Selective inhibitors of iNOS would therefore be a useful approach to the treatment of inflammatory diseases and pain. As a part of our research program in this area, a series of novel imidazolepyrimidines was designed and synthesized as potent inhibitors of iNOS dimer formation, a key prerequisite for proper functioning of the enzyme. The details of the synthesis and the biological activity of these novel iNOS dimerization inhibitors will be presented.