Further work suggests that methylxanthines may interfere with the therapeutic efficacy of neuroleptics, since the catalepsy induced by haloperidol or chlorpromazine is reversed by methylxanthines. However, these works are done through the acute administration of drugs, which excludes the possible development of tolerance to methylxanthines. In the present work a review of the literature was made and it was observed that the studies on the development of tolerance to methylxanthines are few and, in some cases, controversial. In addition, in our laboratory, we did not find caffeine tolerance regarding the stimulation of locomotor activity and the reversal of chlorpromazine-induced catalepsy