Summary In the last decade reliable methods have been introduced to quantitate and characterize receptors for hormones and other biologically interesting ligands. Applied initially to hormone receptors on malignant cells and to androgen-resistant and insulin-resistant states, these methods have led to the identification of many disease processes where the receptor plays an important role. This includes not only endocrine-related diseases but also neurological, metabolic, infectious, and immune disorders as well. Note. On the basis of biological and chemical data, it appears that the 40 to 50 different hormones found in a given organism each evolved from a much smaller number of primordial hormones. Presumably, for the peptide hormones the gene for the primordial hormone was duplicated as was the gene for its cell surface receptor; the new hormone-receptor pair evolved to establish a second signaling system. The affinity of each hormone for its specific receptor was high but in many cases the ligand retained some finite (albeit low) affinity for the other receptor. Thus, teleologically, greater diversity was paid for by a small loss in specificity. The weak affinity of one hormone for the receptor of a closely related hormone forms the basis for specificity spillover. The modest impairment of specificity in endocrine systems, its postulated origins, and suggested consequences may have significant counterparts in other areas of biology where diversity coexists with modest degeneracies in specificity, e.g., the large series of trypsin-like proteases that regulate multiple extracellular events such as clotting and kinin generation; neurotransmitters and related drugs; cyclase and the nucleotide-stimulated kinases; autoantibodies and prostaglandins.