Although much of our knowledge of the pharmacological response of the urinary bladder comes from in vitro muscle strip studies, it is not clear if these studies can be directly correlated with bladder function. We have compared the pharmacological response of an in vitro whole bladder model with the response of the standard muscle strip technique. The whole bladder model has the advantage of being able to measure both the isometric contractile response to drugs as well as a functional response in which the bladder can empty in the presence of a constant resistance. The results of these studies may be summarized as follows: 1) bethanechol was equipotent in contracting the muscle strips and in the closed whole bladder model; 2) at low and intermediate bladder volumes, the bladder fully emptied at concentrations of bethanechol significantly below the concentration required for maximal contraction; 3) isoproterenol, a potent beta-adrenergic agonist, stimulated a strong relaxation in muscle strips, whereas the whole bladder responded very poorly to isoproterenol; 4) in muscle strips isoproterenol strongly antagonized bethanechol contraction, whereas, in the whole bladder system, isoproterenol did not significantly antagonize bethanechol contraction; 5) methoxamine and adenosine triphosphate produced a moderate, equipotent contraction in both models.