The effects of 10 days treatment with haloperidol or sulpiride on tissue levels of neurokinin A-like and substance P-like immunoreactivity (NKA-LI and SP-LI) in various regions of rat brain were studied using reversed phase HPLC and radioimmunoassay. The most marked effect was a decrease in NKA-LI levels in n.accumbens after treatment with both sulpiride and haloperidol. Striatal NKA-LI and SP-LI levels were not clearly affected. NKA-LI levels but not SP-LI levels were decreased in substantia nigra by haloperidol. A low dose of sulpiride increased both NKA-LI and SP-LI levels in ventral tegmental area/n.interpeduncularis. In conclusion, region-specific changes of NKA-LI and SP-LI were seen after subchronic treatment with neuroleptics. It seems likely that NKA and SP are involved in the neuronal adaptation to the repeated treatment with neuroleptics.