Infusion of the long-acting beta-adrenergic agonist ritodrine (3 micrograms/kg/min) caused by rapid inhibition of uterine activity in the ovariectomized, nonpregnant sheep. This inhibition could only be maintained for 6.4 +/- 0.8 hours, with high-frequency activity returning by 11.4 +/- 2.6 hours despite continuous infusion of ritodrine. Intermittent administration of ritodrine did not prolong uterine relaxation, probably as a consequence of its long half-life. Continuous infusion of the short-acting beta-agonist isoproterenol (0.16 micrograms/kg/min) initially inhibited uterine contractions but high-frequency activity returned by 50 minutes. In contrast, intermittent infusion of isoproterenol (30 minutes on and 30 minutes off) significantly inhibited the frequency of contractions during each of the infusion periods for the duration of the study (13 hours). Our data demonstrate that either continuous administration of beta-agonists or intermittent administration of the long-acting beta-agonist ritodrine resulted in myometrial desensitization in the sheep. In contrast, intermittent administration of the short-acting beta-adrenergic agonist isoproterenol prevented the onset of myometrial desensitization.