The possibility that the liver plays a role in the growth-promoting actions of PRL on the mammary lobuloalveolar (L-A) system was investigated using 6-week-old female rats. Chronic indwelling catheters were inserted into the external jugular vein (EJV) or the hepatic portal vein (HPV) and attached to osmotic minipumps, which were used to infuse pulses of ovine (o) PRL (4/day of 2 h each, total dose = 20 micrograms/day) for 14 days. The rats were hypophysectomized 2 days after catheterization, and given daily sc injections of estradiol + progesterone in oil (2 micrograms and 5 mg/day, respectively) plus twice daily ip injections of porcine GH (50 micrograms/injection) from days 2-13. They were killed on day 14. Controls received the sc and ip hormone injections but were given solvent infusion into the EJV or the HPV instead of oPRL. Infusion of the oPRL into the EJV did not promote mammary L-A growth more than did infusion of solvent into either the EJV or the HPV. By contrast, infusion of the same dose of the hormone into the HPV caused a significant stimulation of the L-A growth. Serum insulin-like growth factor-I (IGF-I) levels were measured by RIA in the rats given the same hormone injections with either intrahepatic infusion of solvent or oPRL, but terminated 7 days after the start of infusion. Intrahepatic delivery of oPRL was not more effective at elevating serum IGF-I concentrations than was the infusion of solvent. These results indicate that the liver may participate in the mammotrophic actions of PRL and serum IGF-I is not responsible for this effect.