Neuropeptide FF (NPFF) is a neuropeptide with antiopiate properties able to antagonize the action of both endogenous and exogenous opiates. Because we have recently shown that NPFF modulates the proliferation of human T lymphocytes, we have searched for binding sites for this peptide on T lymphocytes. Our study shows that T lymphocytes of the Jurkat cell line express binding sites for [125I]YLFQPQRFamide, an iodinated analogue of NPFF. This binding is time and dose dependent, reversible, saturable, and may be resolved in two distinct components of high and low affinity. The opiate receptor agonists mu, delta, and kappa, as well the antagonist naloxone, were unable to affect binding. Beside the effects of opiates on immune cells, our results suggest that an antiopiate peptide, such as NPFF, could play a role in the modulation of the immune system.