A single i.p. injection of 10 nmol of a monoclonal antibody to progesterone (mAb-P4) on Day 4 of pregnancy (day of nidation) interrupts pregnancy by Day 8 (Day 1 = sperm-positive smear) in 75% of treated hamsters (n = 8). This correlates with structural and functional luteolysis, significantly (p < 0.05) reduced serum prolactin (PRL), and a nonsignificant trend for reduced FSH (which constitute the minimal luteotropic complex of the hamster), but LH is unchanged. Embryos implant and develop normally for a while, but by Day 8 the uterus is distended with the resorbing products of conception. The abortifacient effects of passive immunization against progesterone are reversed 100% by s.c. injection of 100 micrograms PRL daily on Days 4-7; deferring PRL treatment until Days 6-7 maintained pregnancy in 75% of the animals, still significantly different from the untreated mAb-P4 group. Injection of 50 micrograms PRL on Days 4-7 maintains pregnancy in 50% of the mAb-P4-treated hamsters (not significantly different), whereas 10 micrograms PRL on Days 4-7 is wholly ineffective. No dose of FSH (0.1-10.0 micrograms) or LH (0.4-2.0 micrograms) on Days 4-7 reversed the effects of mAb-P4; neither did 10 micrograms PRL plus 0.4 or 2 micrograms of FSH. The maintenance of pregnancy after 100 micrograms PRL on Days 4-7 is associated with normal serum levels of PRL, FSH, and LH and no change in the serum concentration of the mAb-P4 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)