Dynorphin A (Dyn A), an endogenous opioid peptide that preferentially interacts with κ-opioid receptors but also exhibits affinity for μ- and δ-opioid binding sites, has been structurally modified to identify analogues with enhanced κ-receptor selectivity. As part of efforts to develop selective and potent κ-receptor antagonists, N-monoalkylated [D-Pro¹⁰]Dyn A-(1-11) analogues (with R = allyl, cyclopropylmethyl (CPM), or benzyl at the N-terminal tyrosine position) were synthesized via solid-phase peptide synthesis. Radioligand binding assays showed these N-monoalkylated analogues retained κ-receptor affinity similar to the parent peptide [D-Pro¹⁰]Dyn A-(1-11) but markedly decreased affinities for μ- and δ-opioid sites, resulting in exceptionally κ-selective peptides—with selectivities equal to or greater than those of the κ-selective nonpeptide agonists U-50,488 and U-69,593, and higher κ-affinities. In contrast, introduction of a second allyl group to form the N,N-diallyl analogue decreased κ-receptor affinity 73-fold and significantly reduced κ-selectivity. Guinea pig ileum (GPI) assays revealed agonist potency varied with N-terminal substituents: N-allyl and N-CPM analogues were moderately potent agonists, while N-benzyl and N,N-diallyl analogues were weak agonists. These N-monoalkylated [D-Pro¹⁰]Dyn A-(1-11) derivatives are the most κ-selective opioid peptides reported to date and should be useful tools for studying the structure and functions of κ-opioid receptors. The low κ-receptor affinity and selectivity of the N,N-diallyl derivative result from the second allyl substituent on the amine terminus.