Possible roles for neutrophils in the response of sensitized rat uteri to a deciduogenic stimulus were investigated. Ovariectomized rats were sensitized for the decidual cell reaction by the administration of estradiol and progesterone. Sesame oil was injected into one uterine horn as a deciduogenic stimulus on the equivalent of Day 5 of pseudopregnancy. Neutrophil numbers in the endometrium, as determined by microscopy after application of the stimulus, were dependent on time and stimulation. Very few neutrophils were found in the endometrium before stimulation. To determine whether neutrophils were involved in the uterine responses to a deciduogenic stimulus, rats were depleted of circulating neutrophils by prior treatment with either methotrexate (MET) or antineutrophil serum (ANS). The increase in endometrial vascular permeability, as quantified with [I-125]-BSA 10 h after stimulation, was not significantly affected by MET or ANS treatment, nor was the extent of decidualization, as indicated by the weight of the uteri 5 days after stimulation. Endometrial neutrophil numbers were significantly lower in the MET- and ANS-treated animals compared to their respective controls. In the uterus, activity of mycloperoxidase, an enzyme found mainly in neutrophils, was significantly reduced in MET-treated animals. To investigate the role of neutrophils in blastocyst implantation, we treated rats with ANS early on Day 5 of pregnancy. On Day 6, neither the numbers of implantation sites nor their weights were affected by ANS treatment. ANS treatment on Day 5 of pregnancy did not attenuate the numbers and weights of placentae and fetuses on Days 19 and 20 of pregnancy. These results indicate that treatments that substantially reduce endometrial neutrophil numbers for at least 30 h around the time of the initiation of implantation/decidualization did not affect the process of implantation/decidualization.