Five neuroleptics: penfluridol, haloperidol, chlorpromazine, pimozide and oxypertine, and two benzodiazepine minor tranquilizers; chlordiazepoxide and diazepam, were studied in mice and rats. When the drugs were injected i.p. in mice, all neuroleptics increased the brain homovanillic acid (HVA) concentration but two benzodiazepines did not change it. Of the drugs tested, only pimozide increased the brain level of 5-hydroxyindoleacetic acid. Penfluridol accelerated the turnover rate of brain dopamine (DA), wheras haloperidol accelerated both DA and noradrenaline turnover rates. In rats, oral administration of penfluridol caused an increase in the striatal HVA and 3,4-dihydroxyphenylacetic acid which persisted longer than that following haloperidol. The concentration of brain 3-methoxy-4-hydroxyphenylethylene glycol, however, was not affected by penfluridol even when the drug was administered at a high dose. Based on these and earlier findings, it is concluded that the effect of penfluridol on DA metabolism resembles that of typical neuroleptic compounds and penfluridol acts only on DA neurons as a long-acting DA receptor blocker.