In rats, the continuous infusion of ACTH-(1-24) into a brain lateral ventricle (0.5 micrograms/h in the volume of 1.11 microliters, for 7 days) caused a significant inhibition of the subsequent behavioural response to the acute intracerebroventricular injection of the same peptide. Tolerance developed to all the most typical signs of the ACTH-induced behavioural syndrome (grooming, stretching, yawning, penile erection, inhibition of food intake), and was associated with a significant increase in the hypothalamic levels of beta-endorphin immunoreactivity.