Previous work has demonstrated that repeated applications of capsaicin can sensitize the tongue to subsequent exposures to capsaicin. However, if stimulation is interrupted for a period of minutes, the contrasting phenomenon of desensitization occurs. The purpose of the present study was to investigate the effect of interstimulus interval (ISI) on the development of both sensitization and desensitization to sequential capsaicin stimuli. It was determined in the first experiment that the rate of sensitization varied inversely with ISI for intervals briefer than 3.5 min; when ISI was lengthened to 5.5 min, sensitization was replaced by a trend toward desensitization. A second experiment established that increasing ISI from 9.5 min to 14.5 min tended to reduce rather than to enhance desensitization. It was therefore concluded that the sensitization process can be optimized by decreasing the time between successive stimuli (ISIs less than 3.5 min), whereas the trend toward desensitization appears to be optimal when stimuli are separated by at least 5.5 min but by less than 14.5 min.