The present study addressed the question of whether the effects of neuropeptide Y (NPY) on parameters of cellular immune activity are mediated by the direct action of this neuropeptide on lymphocyte NPY receptors. A partial cDNA corresponding to bp 3-585 of the NPY-Y1 receptor coding sequence was cloned from rat splenic lymphocytes and found to have 100% nucleotide sequence homology with that segment of the NPY-Y1 receptor in brain. Basal levels of NPY-Y1 mRNA expression and [125I]NPY binding sites of rat splenic lymphocytes were markedly lower than in frontal cortex. These data provide the first direct evidence that cells of the immune system possess NPY receptors, and suggest that further study will be necessary to determine their physiological significance.