OBJECTIVE This study was designed to determine if dexamethasone alters myometrial responsiveness to oxytocin or oxytocin secretion. METHODS Studies were conducted in rhesus macaques (n = 6), between 144 and 148 days' gestation (term 167 days). The first study was conducted at 9 AM and repeated 36 hours later at 9 PM. At 9 AM the following morning a continuous maternal dexamethasone infusion (15 micrograms/kg/hr given intravenously) was initiated, and the study was repeated at 9 PM, 60 hours later. Four doses of oxytocin (500, 1000, 2000, and 4000 pg/kg/min) were administered as 1-minute pulses every 5 minutes for 30 minutes. The number of contractions per pulse (contraction/pulse ratio) was used to determine differences in myometrial responsiveness. RESULTS Before dexamethasone infusion there was a circadian rhythm in uterine activity with peak contractile events between 8 and 10 PM (p < 0.01), whereas during infusion the rhythm was ablated. At oxytocin dose 1, the 9 AM contraction/pulse ratio (0.3 +/- 0.1) was lower than that for 9 PM (0.6 +/- 0.2) and for 60 hours later (0.6 +/- 0.1) (mean +/- SE, p < 0.05). Similar results were observed at dose 2, whereas no differences in the contraction/pulse ratio were noted at dose 3. Basal plasma oxytocin concentrations were unaffected by dexamethasone treatment, whereas plasma estradiol and cortisol concentrations were reduced compared with control values (p < 0.01). CONCLUSIONS (1) There is a differential sensitivity to oxytocin between morning and evening and (2) the dexamethasone-induced loss of the uterine contractile rhythm is not the result of a loss of myometrial sensitivity to oxytocin or to a suppression of plasma oxytocin concentrations.