Capsaicin, the primary pungent principle in hot peppers, produces marked alterations in the function of unmyelinated sensory afferent fibers, which are believed to signal pain and to initiate inflammatory responses. Capsaicin first excites and then desensitizes these nerves to subsequent stimulation both by itself and by a variety of physicochemical stimuli. Accordingly, capsaicin is finding increasing use as a topical therapy for a variety of cutaneous disorders that involve pain and inflammation. Although topical capsaicin has shown therapeutic potential, the utility of capsaicin appears to be limited at present primarily by its irritant properties and secondarily by less than optimal therapeutic response, perhaps resulting from insufficient drug delivery. A capsaicin analogue with diminished irritant properties that retained the critical pharmacologic activities might present a reasonable alternative.