The present study was designed to investigate the possible modulator effect of melatonin on uterine estrogen and progesterone receptors in rats as well as the uterine response to oxytocin. Non-pregnant rats were pretreated with melatonin in a dose of 0.8 mg kg(-1) per day for 15 consecutive days. Control animals received the vehicle. The uterus was dissected out and uterine contraction in one horne, as recorded in vitro for each animal as a response to oxytocin (0.5 x 10(-11) to 2 x 10(-11) M). The other uterine horne was Subjected to estrogen and progesterone receptors detection by immunohistochemical and image analysis techniques. The results reveal a significant reduction (59%) in the number of uterine estrogen receptors with concomitant increase in the progesterone receptors (53%) in melatonin-pretreated rats as compared to the control ones. In addition. our data show an inhibitory effect of melatonin on the uterine contraction as a response to oxytocin (0.5 x 10(-11), 1 x 10(-11). and 2 x 10(-11) M) amounting to 48. 77. and 59.5% reduction. respectively, in the amplitude of contraction as well as 62. 19.9, and 47% reduction in the area under the curve (AUC) of uterine contractions, respectively. The data, so far obtained, may indicate a possible relationship of melatonin-induced modulation of the number of estrogen and progesterone receptors and its inhibitory effect on uterine contraction. These findings merit further investigation,., on the possible beneficial role of melatonin in a plethora of hormone-dependant uterine disorders. (C) 2003 Elsevier Science Ltd. All rights reserved.