Anti-progesterone monoclonal antibody prevents the establishment of pregnancy in BALB/c mice by the prevention of implantation when injected i.p. 32 h after mating. To determine the specificity of this effect, mice were injected with immune and non-immune purified mouse immunoglobulins. The results show that anti-implantation efficacy was due to high-affinity antibody which bound progesterone since two further mouse immunoglobulin (Ig) G1 preparations, mouse IgA and mouse IgM which failed to bind the steroid, had no effect on pregnancy rates. From a panel of anti-progesterone monoclonal antibodies, six with a high affinity (affinity constant, 0.24-0.80 litres/nmol) and specificity for progesterone were selected for additional studies. Anti-implantation efficacy for five antibodies was similar, with a 50% effective dose within the range of 0.8-2.0 nmol. Antibody reached high concentrations in plasma within 12 h after i.p. injection, and declined with a half-life of about 80 h. Purified F(ab')2 fragments of antibody also bound progesterone, but were less effective than the native molecule in blocking pregnancy. The results show that implantation in the mouse can be blocked by a high-affinity antibody that binds progesterone and which is removed from the blood at a slow rate.