Treatment of pregnant mice ovariectomized on day 3 (23.00-2330 h) with progesterone (1 mg/day/mouse, from day 4 through 11 post coitum (p.c.)) and oestrogen (single injection of 0.05 mug on day 8 p.c.) induced implantation in all the animals. Implantation was inhibited in animals following three subcutaneous injections of indomethacin given on the morning and afternoon of day 8 and the morning of day 9 p.c. A single injection of histamine on day 8 p.c. partially compensated the effect of indomethacin. A complete reversal of the antifertility effect of indomethacin was achieved following intraperitoneal administration of histamine (2 mug at noon of day 8 p.c.) and PGF2alpha (20 mug on the morning and afternoon of day 8 p.c.). This study suggests that in the mouse uterus indomethacin impairs the physiological changes which are required for the decidual cell formation and implantation. It is likely that an injection of oestradiol in the progesterone treated ovariectomized mice triggers the release of PGF2alpha and histamine and that these compounds are involved in the chain of events leading to implantation of blastocysts.