Three experiments were conducted to examine gene expression during induced luteal regression in the cow; the initial purpose was the identification of potential embryotoxins. In experiment 1, changes in gene expression in the corpus luteum (CL) were identified by differential display reverse transcription-polymerase chain reaction (DD-PCR) during the first 72 h of luteal regression in cows treated with prostaglandin F(2alpha) (PGF(2alpha)) on Days 4-7 after estrus. Expression of insulin-like growth factor-binding protein-1 (IGFBP-1) was up-regulated, with greatest expression at 24 h (P < 0.05) after treatment with PGF(2alpha) began. In experiment. 2, IGFBP-1 and its mRNA were quantified in CL collected 24 or 48 h after treatment with PGF(2alpha) on Day 4 or 10 after estrus. Because local mechanisms for exchange of hormones between the ovary and uterus are known in ruminants, uterine flushings were assayed for IGFBP-1 to seek evidence of local transfer of luteal IGFBP-1 to the uterus. IGFBP-1 mRNA was increased (P < 0.05) in CL 24 h after treatment when PGF(2alpha) that began on Day 10, and by 48 h after treatment that began on Day 4. Concentrations of IGFBP-1 increased (P < 0.05) in a pattern similar to mRNA, by 24 h on Day 10, and by 48 h on Day 4. Concentrations of IGFBP-1 in uterine flushings did not change on either day. Concentrations of progesterone decreased (P < 0.05) by 8 h after treatment with PGF(2alpha) that began on Day 10, but not until 24 h after treatment that began on Day 4. In experiment 3, cows received either saline or PGF(2alpha) and CL were collected 2 or 10 h after a single treatment, or 2 h after a second treatment that was given 8 h after the first. Expression of IGFBP-1 was increased by 2 h after treatment with PGF(2alpha) on both Days 4 and 10 after estrus. In conclusion, secretion of IGFBP-1 is increased during luteolysis, and may inhibit the steroidogenic effects of insulin-like growth factor-I (IGF-I), but no evidence was found to implicate IGFBP-1 in the embryotoxic effect of regressing CL.