Neuropeptide Y (NPY) is known to bind to at least two types of receptors (Y1 & Y2). One type (Y2) is able to bind and undergo activation by both NPY and its C-terminal fragments with good potency while the other (Y1) requires the full length of NPY for good potency. For most NPY analogs that have been examined, potency for the Y2 system (porcine spleen) is greater than or equal to that for the Y1 system (mouse brain), since the Y2 system is generally less selective. However, modifications of NPY and its analogs at position 34 can lead to materials with some Y1 selectivity. For example, [Pro34]-pNPY binds to mouse brain with an affinity of 0.14 nM. Its affinity for porcine spleen is 140 nM. [His34]-pNPY was also found to be Y1 selective (19-fold), but not to the degree of the [Pro34] analog (1000-fold). The Pro34 modification in the Y2 selective C-terminal fragment NPY (20-36) converted it into an essentially non-selective analog. The selectivity from the Pro34 substitution results from a loss of Y2 binding potency along with little effect on the Y1-receptor binding. Therefore, Y1 and Y2 receptors have differing requirements for the C-terminal region of NPY in addition to their different requirements for NPY's N-terminus.