The present data show that monoclonal antibodies (NPY02, NPY03, NPY04, NPY05) directed against 4 distinct epitopes on NPY may have different actions on NPY binding and NPY-induced cellular responses. NPY02 and NPY05 recognize the 11-24 and 32-36 amidated form of NPY, respectively. These 2 antibodies block the binding of NPY to its receptor as well as the NPY-induced inhibition of cAMP accumulation caused in SK-N-MC cells by forskolin. NPY02 and NPY05 have also an inhibitory action on NPY-induced contraction of rabbit femoral arteries. NPY03 and NPY04 are directed against the 27-34 and 1-12 part of NPY, respectively. NPY03 and NPY04 inhibit the binding of NPY only at very high concentrations and have a weak effect on cAMP response to NPY. NPY02 and NPY05 might provide useful tools to study the effect of NPY in cellular systems and organ preparations.