A stimulus-response coupling model in which individual steps follow hyperbolic or Hill-type laws has been employed to mimic phenomena associated with irreversible receptor inhibition (receptor reserve) in a responding biological system. Two methods for computation of ligand-receptor dissociation constant (KA) have been derived from this model: 1) The relation between pD2 and maximal attainable response allows a rough estimate of KA; 2) A generalization of the earlier Furchgott-Bursztyn procedure employing equipotent doses for noninhibited and partially inhibited systems, has been achieved by introduction of Hill equation into the model. Applied to oxytocin and angiotensin II receptors in rat uterus, these pharmacological methods indicate rather low affinity of the two receptors for the respective peptides (around 2 X 10(-8) for angiotensin II and 2 X 10(-7) mol/l for oxytocin), in case of oxytocin much lower than values reported from binding studies. Apparently, several binding sites are present on the target tissue cells from which the methods based on cellular response can pick up those corresponding to the receptors. Biophysical methods are lacking this ability. Single pD2 values in noninhibited systems cannot themselves deliver any relevant information about receptor binding.