The neuropeptide substance P (SP) is widely distributed within the central nervous system (CNS) and exhibits high affinity for the neurokinin NK-1 receptor but is also present in peripheral tissues. Both N- and C-terminal fragments of SP are shown to retain biological activity. The C-terminal part of SP is known to interact with the NK-1 receptor and fragments containing this sequence mimic several agonistic effects mediated through this receptor. A biologically potent peptide released from the N- terminal portion of SP is SP(1–7). It is formed by enzymatic conversion of SP and it is also found to be present in many areas of the CNS. Studies have shown that SP(1–7) may counteract the expression of opiate tolerance and withdrawal. This is in contrast to what is seen for SP and other NK-1 receptor agonists, which increases the reaction to opioid withdrawal. SP is also known to facilitate nociception by acting on NK-1 receptors at the spinal level, while SP(1–7) in contrast to SP exhibits anti- nociceptive activity. Moreover, whereas SP is shown to potentiate the outcome of peripheral inflammation in a rat blister model the heptapeptide is shown to attenuate the SP-induced response. Recent research in our group suggests that SP(1–7) does not mediate its effects through any of the known tachykinin receptors and not via activation of any opioid receptor. The SP(1–7) fragment rather appears to produce its effects through specific sites for this heptapeptide, which are not recognized by its parent peptide SP. We have characterized specific sites for SP(1–7) in the rat and mouse spinal cord. We now synthesize both peptide and non-peptide analogues of SP(1–7) and study these compounds with regard to their anti-nociceptive and anti- inflammatory properties. Some of these new compounds exhibit binding affinity and functional potency exceeding that of the native compound.