We compared the effect of chronic clozapine and haloperidol treatment on the expression of rat brain vesicular monoamine transporter (VMAT(2)) as well as on the membranal presynaptic transporters for serotonin, dopamine and noradrenaline. Rats were treated for 21 days with clozapine (25 mg/kg), haloperidol (0.5 mg/kg) or saline. VMAT(2) expression was assessed on the protein level by high affinity [3H]dihydrotetrabenazine binding using autoradiography, and on the mRNA level by in situ hybridization. The densities of the monoamine transporters were evaluated by autoradiography using specific ligands. Clozapine administration led to an increase in [3H]TBZOH binding in the nucleus accumbens, prefrontal cortex and striatum, whereas haloperidol had no effect on VMAT(2) binding capacity. The clozapine-induced increase in VMAT(2) was accompanied by a parallel increase in the membrane serotonin transporter in the prefrontal cortex and the striatum. Haloperidol induced an increase in the serotonin transporter in the striatum and the core of the nucleus accumbens. The special effect of clozapine on VMAT(2) expression may be relevant to its unique therapeutic advantages.