Chronic treatment with des-enkephalin-gamma-endorphin (DE gamma E, beta-endorphin 6-17) twice daily for 10 days into the nucleus accumbens of rats resulted in hypoactivity, while similar treatment with gamma-endorphin antiserum led to a marked hyperactivity. This enhanced activity persisted for at least 3 days following discontinuation of treatment. Rats chronically treated with gamma-endorphin antiserum into the nucleus accumbens habituated at a slower rate when tested repeatedly for locomotor activity, as well as for nociception. Passive avoidance behaviour was attenuated in the treated rats, when they were trained during treatment, but not when the learning trial was given before treatment and testing was performed during treatment. Treatment with gamma-endorphin antiserum did not affect the diurnal rhythm in locomotion, the responsiveness to nociceptive stimulation and the basal and novelty stress induced-plasma corticosteroid levels. It is concluded that chronic treatment with gamma-endorphin antiserum into the nucleus accumbens, which may lead to bio-inactivation of gamma-type endorphins, causes hyperactivity and disturbances in habituation and cognitive functions. It is suggested that gamma-type endorphins are physiologically involved in the control of distinct dopaminergic systems in the nucleus accumbens. The findings are discussed in relation to the role of mesolimbic dopaminergic systems in schizophrenic psychosis.