Orexin A and B (also known as hypocretins), two recently discovered neuropeptides, play an important role in food intake, sleep/wake cycle and neuroendocrine functions. Orexins are endogenous ligands of two G-protein-coupled receptors, termed OX1 and OX2. This work presents the first short orexin A and B analogues, orexin A 23–33 and orexin B 18–28, with high affinity (119 ± 49 and 49 ± 23 nM) for OX1 receptors expressed on SK-N-MC cells and indicates the importance of the C-terminal part of the orexin peptides for this ligand–receptor interaction. However, these C-terminal fragments of orexin did not displace the 125 I-labelled.