The phenomenon of "ligand-directed signaling" is often considered to be inconsistent with the traditional receptor theory. In this review, I show how the mathematics of the receptor theory can be used to measure the observed affinity and relative efficacy of protean ligands at G protein-coupled receptors. The basis of this analysis rests on the assumption that the fraction of agonist bound in the form of the active receptor-G protein-guanine nucleotide complex is the biochemical equivalent of the pharmacological stimulus. Consequently, this stimulus function is analogous to the current response of a ligand-gated ion channel. Because guanosine triphosphate (GTP) greatly inhibits the formation of the active quaternary complex, even the most efficacious agonists probably only elicit partial receptor activation, and it seems likely that the ceiling of 100% receptor activation is not reached in the intact cell with high intracellular concentrations of GTP. Under these conditions, the maximum of the stimulus function is proportional to the ratio of microscopic affinity constants of the agonist for ground and active states. Ligand-directed signaling depends on the existence of different active states of the receptor with different selectivities for different G proteins or other effectors. This phenomenon can be characterized using classic pharmacological methods. Although not widely appreciated, it is possible to estimate the product of observed affinity and intrinsic efficacy expressed relative to that of another agonist (intrinsic relative activity) through the analysis of the concentration-response curves. No other information is required. This approach should be useful in quantifying agonist activity and in converting the two disparate parameters of potency and maximal response into a single parameter dependent only on the agonist-receptor-effector complex.