Schild regressions in isolated tissues are powerful tools for receptor classification only if they yield equilibrium dissociation constants of antagonists, which can occur only when measurements are made under equilibrium conditions. Regressions with slopes different from unity or nonlinear regressions indicate noncompliance to equilibrium. A condition whereby Schild regressions apparently comply with criteria which signify equilibrium conditions but are regressions obtained at nonequilibrium steady states yielding significant underestimations of the potency of the antagonist is described. If agonist uptake processes in isolated tissues are inhibited by uptake inhibitors with receptor blocking properties, the experimental data and a theoretical model suggest that the resulting Schild regression will be linear, have a slope of unity and be shifted to the right of the true Schild regression, significantly underestimating antagonist potency. Experiments with the effects of neuronal uptake inhibition (with desmethylimipramine and amitriptylene) on the phentolamine inhibition of norepinephrine responses in rat anococcygeus muscle and the effects of metanephrine on the propranolol inhibition of isoproterenol relaxation of guinea pig trachea provided data to compare to a theoretical model. The data and the model help define the selectivity of the uptake inhibitor for uptake over receptors needed to achieve steady states approaching true equilibrium, a condition required for satisfactory estimation of antagonist potency.