The study of ligand receptor interactions and receptor function often requires multifaceted experimental approaches. In the course of studying the function and mechanism of action of müllerian inhibiting substance (MIS), we have used a wide range of molecular and cellular techniques. These have led to the identification, cloning, and characterization of the MIS receptors and of other receptors for the transforming growth factor-beta (TGF beta) family. This article describes the use of polymerase chain reaction (PCR) cloning to isolate candidate receptor genes, transfection and flow cytometry to study ligand binding, nonhomologous recombination targeted gene disruption (knockout) to analyze receptor function, and yeast genetics to identify other proteins that interact with the receptor complex. Together these techniques have led to the development of therapeutics and therapeutic strategies that are ready for clinical application.