Nitric oxide is produced by the oxidation of the terminal guanidine group of L-arginine by three distinct isoforms of nitric oxide synthase (NOS): the constitutively expressed neuronal NOS (nNOS) and endothelial NOS (eNOS), and the induced isoform - iNOS. Overexpression of iNOS has been implicated in the pathology of a large number of inflammatory diseases. In recent years there has been significant interest in the role of iNOS in the pathophysiology of inflammatory and neuropathic pain. Recent studies indicated that GW274150, a potent and highly selective iNOS inhibitor, exhibits analgesic effects in rat models of inflammatory and neuropathic pain. Selective inhibitors of iNOS may therefore be a useful therapy for the treatment of these diseases. We report the design and synthesis of novel cyclic oxyguanidines as potential iNOS inhibitors. These agents combine the structural features of the iminopiperidine and iminohomopiperidine iNOS inhibitors, and L-canavanine, the naturally occurring oxyguanidine containing iNOS inhibitor.