Although humans frequently develop preferences for innately unpalatable bitter or irritant substances, such preferences are extremely rare in animals. An attempt was made to understand the nature of this difference by systematic experiments with laboratory rats, with chili pepper as the unpalatable substance. In parallel with major aspects of the human experience with chili pepper, rats were exposed to it as a flavoring in all their food for periods up to 11 mo from birth, without significant preference enhancement. Gradual introduction of chili into the diet also had no effect, nor did a series of poisoning and safety experiences designed to teach the rats that only chili-flavored foods were safe to eat. A sequence of seven pairings of chili-flavored diet with prompt recovery from thiamine deficiency did significantly attenuate the innate aversion and may have induced a chili preference in at least one case. Extensive experience with chili did not reliably make rats much less sensitive to its oral effects. The only reliable way to eliminate chili aversion in rats is to destroy their chemical irritant sense, which was accomplished in one group of rats. It is concluded that in contrast to humans, it is extremely difficult to reverse innate aversions in rats.