We measured serum corticosteroid-binding globulin (CBG) and hepatic CBG mRNA from individual hamsters throughout pregnancy and during decidualization. Serum CBG levels were determined by 3H-cortisol binding assay, and hepatic CBG mRNA levels were measured by Northern blots and solution hybridization assays, using a 32P-labeled cRNA probe derived from a rat CBG cDNA. There was a positive relationship between hepatic CBG mRNA levels and serum CBG levels during pregnancy. Both parameters increased significantly from the time of mating (cycle Day 4) to pregnancy Day 4, showing that CBG synthesis and secretion increased prior to implantation (Day 4). After implantation, serum CBG and hepatic CBG mRNA rose further from pregnancy Day 4 to a peak on Day 14, then decreased before parturition on Day 16. The prepartum decline in hepatic CBG mRNA preceded the fall in serum CBG. Decidualization on pseudopregnancy Day 4 resulted in an increase in serum CBG and hepatic CBG mRNA. Hepatic CBG mRNA increased from Day 5 to Day 7, and serum CBG increased progressively from Day 5 through Day 9 after uterine decidualization in the hamster. The present results demonstrate that the pattern of serum CBG observed in the pregnant hamster follows closely that of hepatic CBG mRNA. A signal emanating from uterine decidual tissue appears to be important in the regulation of hepatic CBG synthesis and secretion during midpregnancy, but other unknown factors appear to be involved in controlling CBG during the early and late stages of pregnancy.