We studied the brain uptake of leptin and of a set of peptides whose combined sequences spanned the entire mature human leptin protein. We compared their uptake to that of albumin and IgG. Two of these peptides, consisting of residues 1-33 and 61-90, demonstrated brain uptake on a par with leptin protein itself, and significantly higher than the uptake of albumin and IgG. Further investigation revealed a peptide, 12-32, with higher uptake than its parent peptide 1-33. Peptide 61-90 had the highest brain uptake, and this was shown to be saturable. Comparison of these brain-permeant peptides with the published structure of the leptin:leptin receptor complex revealed a high degree of correlation. All of the leptin residues that have been identified as important receptor-binding contacts appeared to have a role in brain uptake, indicating that receptor binding is an intrinsic part of transport across the blood-brain barrier. The effect of these peptides as leptin agonists or antagonists remains to be investigated. The newly identified peptides also have a potentially large role as carrier molecules for new brain therapeutics, since peptides can be readily coupled to other molecules.