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A central question in protein folding is the relative importance of locally encoded structure and cooperative interactions among residues distant in sequence. We have been exploring this question in a predominantly beta-sheet protein, since beta-structure formation clearly relies on both local and global sequence information. We present evidence that a 24-residue peptide corresponding to two linked hairpins of cellular retinoic acid-binding protein I (CRABP I) adopts significant native structure in aqueous solution. Prior work from our laboratory showed that the two turns contained in this fragment (turns III and IV) had the highest tendency of any of the eight turns in this anti-parallel beta-barrel to fold into native turns. In addition, the primary sequence of these two turns is well conserved throughout the structural family to which CRABP I belongs, and residues in the turns and their associated hairpins participate in a network of conserved long-range interactions. We propose that the strong local-sequence biases within the chain segment comprising turns III and IV favor longer-range interactions that are crucial to the folding and native-state stability of CRABP I, and may play a similar role in related intracellular lipid-binding proteins (iLBPs).