Soon after ovulation, the corpus luteum (CL) starts secreting progesterone (P(4)), a hormone necessary for implantation. The aim of the study was to evaluate whether P(4) exerts an autocrine/paracrine action on luteal angiogenic activity and P(4), prostaglandin E(2) (PGE(2)) and NO production in the mare. Corpora hemorrhagica (CH) and mid-luteal phase CL (MCL) were cultured with (i) no hormone (Control); (ii) P(4); (iii) a P(4) precursor - pregnenolone; or (iv) a P(4) antagonist - onapristone [10(-4) M;10(-5) M; all steroids]. NO production decreased in MCL, with respect to CH, when treated with P(4) [10(-4) M] and pregnenolone [10(-5) M]. PGE(2) increased from CH to MCL, and showed a tendency to rise in pregnenolone treated luteal tissues (10(-4) M; p=0.06). In the CH, P(4) decreased with pregnenolone [10(-4) M] compared to control, P(4) [10(-5) M], onapristone [10(-4) M;10(-5) M] and pregnenolone [10(-5) M](p<0.05). In the MCL, pregnenolone [10(-5) M] decreased (p<0.05) and P(4) tended to decrease (p=0.06) bovine aortic endothelial cell (BAEC) mitogenesis. Onapristone [10(-4) M] increased BAEC proliferation with respect to P(4) (p=0.01). Since there was no direct effect of treatments on BAEC, these data suggest that long-lasting effects of P(4) and its precursor may inhibit angiogenic factor(s) production by equine MCL, preparing for CL functional and structural regression.