In classical occupancy receptor theory, efficacy is a dimensionless proport
ionality constant denoting the power of agonists to produce a pharmacologic
al response. In theoretical terms, it is difficult to separate affinity and
efficacy estimates of agonists for receptors, hence questioning the value
of clearly flawed estimates of efficacy by conventional methods. In this pa
per, the use of efficacy estimates, the limitations of the current methods
to estimate efficacy, and the types of systems in which serious errors in e
fficacy estimation would be expected, is discussed. Specifically, in consti
tutively active receptor systems or in those where the receptor interacts w
ith more than one G protein, there are theoretical objections to the use of
relative maximal responses as indicators of intrinsic efficacy of agonists
.