Asymmetrical modulation of immune reactivity by central dopaminergic pathways was suggested by previous reports which described an association between alterations of immune response and peculiar patterns of dopamine asymmetries in pathological and physiological situations. In the present experiments, we studied the respective roles of the nigrostriatal and mesolimbic dopaminergic networks in the asymmetrical modulation of immune responses. Lymphocyte proliferation as well as natural killer (NK) cell activity were analysed in mice, 2 weeks after unilateral lesions of dopaminergic projections by in situ injection of 6-hydroxydopamine in the striatum or the nucleus accumbens. After lesions of the striatum, proliferation of splenic lymphocytes was impaired only in the right-lesioned group. Left-lesions appeared to not modify T lymphocyte reactivity. After lesions of the nucleus accumbens, no modification of T lymphocyte mitogenesis was observed but splenic NK cell activity was depressed in left-lesioned mice as compared with controls or right-lesioned animals. Proliferation of B lymphocytes was not affected by striatal or mesolimbic dopaminergic lesions. It was concluded that both striatal and mesolimbic dopaminergic pathways are asymmetrically involved in neuro-immunomodulation. These dopaminergic regions appear to function independently as the effective side as well as the immune parameters that were altered differ according to the structure lesioned.