Previous work in this laboratory has demonstrated that the bladders of 1-day-old and 1-week-old rabbits generate higher pressures in whole-bladder preparations than bladders from mature 8-week-old rabbits. In addition, the density of cholinergic receptors does not change during this maturation period. The present study was designed to determine if the increased responsiveness of the neonatal bladder was specific for cholinergic stimulation. Using bladder strips, we have demonstrated that the newborn bladders generated much greater tension in response to ATP, serotonin, histamine, and substance P. The response of the 1-day-old bladder smooth muscle to these contractile agents was at least double the response of the 8-week-old bladders. However, the response of all age groups to bethanechol was approximately the same, and the response to KCl was only 40% greater in the 1-day-old bladders as compared to the adult. These current studies indicate that the newborn bladder responds to a variety of nonadrenergic, noncholinergic agonists to a significantly higher degree than the adult bladder, and that maturation is accompanied by substantial changes in the pharmacology of the bladder.