A standard rabbit thoracic-aorta strip preparation was used to determine the effect of varying preload on KA (the dissociation constant), A50(the concentration that produces half maximal response) and the ratio KA/A50. The stimulus-response relationships were obtained for the drug and preload conditions tested. Values of KA and A50 were calculated from dose-response curves obtained for 3 .alpha.-adrenergic agonists (phenylephrine, methoxamine and norepinephrine) in the presence and absence of partial irreversible blockade by phenoxybenzamine. For all 3 drugs, values of KA and A50 were significantly greater at 1/4 g preload than at 10 g preload. The ratio KA/A50 was independent of preload conditions. The stimulus-response relationships were non-linear, in contrast to the predictions of classical receptor theory. The significance of the constancy of KA/A50, rather than KA or A50, and the non-linear relation between drug stimulus and response are discussed in terms of Stephenson''s theory of drug action.