In schizophrenic brain, an increased level of norepinephrine and decreased level of met-enkephalin have been detected. The pathogenic significance of these factors is unknown. The present study assessed the influence of the combination of these factors on serotonergic 2A (5-HT_2A) receptors which are possibly related to the development of hallucinations. The experiments were conducted on male Wistar rats. The decrease in brain enkephalinergic activity was simulated by injections of naloxone, and the frequency of head twitches was used as an index of 5-HT_2A receptor activity. Norepinephrine (i.c.v.) and naloxone (i.p.) alone produced no behavioral effects; however, the combination of the drugs initiated distinct head twitch response. The combination effect was reversed by MDL 100907, an antagonist of 5-HT_2A receptors, and clonidine, an agonist of α₂-adrenoceptors. These findings may provide novel insight into the mechanism of 5-HT_2A-receptor-mediated processes. In light of the presented data, simultaneous manipulations of α- and opioid δ/µ- receptors might be an approach for therapy of schizophrenic hallucinations.