This study investigated possible neurochemical differences in the brain of two inbred mouse strains, C57BL/6J (C57) and DBA/2J (DBA) that in behavioral, memorization and learning tasks under normal and experimental conditions perform differently or often in an opposite manner. The immunohistochemical study, designed to investigate the dopaminergic system, identified many differences within the midbrain A10 area and less marked differences in areas A9 and A8. The number of dopamine transporter (DAT), vesicular monoamine transporter of type 2 (VMT) and tyrosine hydroxylase (TH) immunoreactive cell bodies was significantly higher in the midbrain of DBA mice than in C57 mice (on average +21.5%, P<0.001 in A10: +9.4% in A9, P<0.05: and +5.9% in A8, P<0.1). The distribution patterns of nerve fibres immunoreactive for same antisera also differed significantly in the two strains, especially at prelimbic, infralimbic and anterior cingulate cortical levels. In C57 mice these fibres were scanty whereas in DBA mice they were well represented. In the nucleus accumbens, also the territorial distribution of DAT immunoreactive nerve fibres differed in the two strains. In the midbrain, the galanin immunoreactive axons were more densely distributed in DBA than in C57 mice whereas neurotensin immunoreactive axons were more densely distributed in C57 than in DBA. These distinct immunohistochemical patterns could help to explain why performance differs in the two mouse strains.