We examined consecutive contractile responses of isolated rabbit pulmonary arteries during repeated exposures to either norepinephrine, histamine or KC1, with washout and relaxation between trials. For each agonist, EC50 values remained constant during consecutive determinations, but the maximum force increased after the first determination. A maximum concentration of norepinephrine or histamine produced a biphasic contraction: the fast phase increased subsequent to the first determination and was retained in a calcium-free medium, while the slow phase was unaltered during consecutive determinations and was absent in a calcium-free medium. We conclude that in the rabbit pulmonary artery: the initial contractile response is a useful control for studies of sensitivity but not of maximum activity; there may be a nonspecific increase in the availability of intracellular calcium after the initial contraction and relaxation, and desensitization or tachyphylaxis to these agonists does not occur.