The D₁-like dopamine receptors have been implicated in the etiology of several neurological and psychiatric disorders. Recent advances in neurobiology have demonstrated the potential utility of D ₁-like dopamine receptor agonists as therapeutic compounds. Despite immense promise, there are no D₁ centrally available agonists currently available as therapeutic compounds. Moreover, there are no selective ligands that can distinguish between the two D₁-like receptors (D ₁ and D₅). One of the major obstacles to the discovery of such agents is limited information about the structural basis for ligand-binding and activation of the D₁-like receptors. There are few such studies that have been done with the D₁ receptor, and virtually none with the D₅ receptor. This dissertation was aimed at gaining a greater understanding of the structural mechanisms necessary for ligand-binding, receptor activation, and receptor internalization. Rationally-selected point mutations of the D₁-like receptors were made, and detailed analysis of binding and function made for a series of structurally and functionally diverse test compounds. Work in this dissertation provides the first experimental evidence that T3.37 plays an important role in binding and activation of D₁-like receptors. Studies of a TM6 phenylalanine at residue at position 6.51 revealed that this residue plays a key role in coupling ligand binding to receptor activation. Studies of another aromatic residue located in TM6, W6.48, provided evidence that this amino acid serves as an important switch residue for creating an active receptor conformational state. Furthermore, this work revealed what may be the largest structural differences ever seen between the D₁ and D₅ receptor subtypes. Results from this dissertation provide important insight into the structural mechanisms that govern ligand-binding and receptor activation, and may aid in the design of clinically relevant D₁ agonists.