The endocrine and immune systems modulate ovarian function. The aim of the present work was to compare the status of various modulating factors in two well-defined stages of corpus luteum (CL) development (the functional stage and the regressing stage) by means of a gonadotropin-synchronised mouse model. At the regressing stage of CL development, we found that ovarian tissue showed increased prostaglandin (PG) F(2alpha) and diminished PGE levels concomitantly with enhanced protein abundance of ovarian cyclooxygenase 2, the inducible isoform of the limiting enzyme of PG synthesis. We also found both enhanced lipid peroxidation and enhanced total superoxide dismutase activity, as well as inhibited catalase activity and inhibited total hydroxyl radical scavenger capacity, when compared with ovaries at the functional stage. In addition, at the regressing stage we observed an increased percentage of CD8+ (cytotoxic/suppressor) T-cells and a decreased percentage of CD4+ (helper) T-cells from ovarian-draining lymph nodes. Also, the serum interleukin (IL)-2, IL-4 and IL-10 were diminished as compared with the functional stage. We conclude that a pro-oxidant status together with a pro-inflammatory response is responsible for the loss of luteal function.