The effects of subchronicly administered neuropeptide Y (NPY) intracerebroventricularly on behavioral, neurochemical, and immunological parameters were examined in sham operated and olfactory bulbectomized (OB) rats. In the untreated OB rats, an increase in ambulation, rearing, grooming, and defecation scores was found in the novel stressful environment of an "open field." Following 7 days of NPY administration, these behaviors were largely attenuated. In the elevated plus-maze apparatus, OB rats showed an increase in the number of entries into the open arms and time spent on the open arms compared with sham operated animals; NPY had no significant effect on the behavior of either sham operated or OB animals in this test. A decrease in the NA concentration was found in the amygdloid cortex of OB rats. NPY infusion significantly increased the NA concentration in amygdala, reduced 5-HIAA but increased 5-HT concentrations in the hypothalamus, and increased the dopamine level in the hippocampus. NPY administration also reversed the suppression of lymphocyte proliferation in the OB rat. However, the changes in the differential white blood cell count and the elevated phytohemagglutinin-induced chemiluminescence of mononuclear cells in the OB were not altered by NPY. These results suggest that NPY may have a modulatory effect on some behavioral, neurotransmitter, and immune aspects of the OB rat model of depression.