Metabolism of capsaicin, the pungent principle of the fruits of Capsicum annuum L., was reported to be brought about by mixed function oxdase of rat liver microsome which was inducible by sodium phenobarbital and inhibited by o-phenanthroline. The metabolite was characterized by U. V. and GC-Mass spectroscopy and by treatment by Ag₂O to be C_5 hydroxylated product: trans-g-methyl-N-(5-hydroxyvanillyl)-nonenamide. Metabolism of capsaicin and its synthetic analogs (capsaicinoids) was investigated to correlate the structure activity relationship of substrate arid the metabolizing ezyme. The results obtained substantiate the recent hypothesis involving two domian nature of NADPH-cytochrome P-450 reductase which was proposed by Gum and Strobel, Fed. Proc. 38,659 (1979). Reduction in the hydrophobic to hydorphilic character ratio in the substrates resulted in gradual reduction in the metabolism and finally no metabolite was observed for the analogs with side chain of five carbon length. Presence of acetamide moiety in close proximity to the aromatic ring showed inhibitory effect and the methylation of the C-4 phenol resulted in complete inhibition of the metabolism.