Growth hormone (GH) acts on various organs to exert its growth and metabolic effects. GH induces transcription of a number of genes in different organs including liver. By performing subtractive hybridization analysis on liver cDNAs of GH transgenic and non-transgenic mice, differentially expressed cDNAs were obtained. This paper describes the isolation and characterization of a liver cDNA, termed cDNA #5, that contains 1897 bp and is predicted to encode a protein (P5) of 512 aa residues. P5 has five immunoglobulin related domains thus allowing it to be classified as a member of the immunoglobulin super family (IGSF). Also, P5 shows significant similarity to both rat and human alpha-1-B glycoprotein which is an acidic serum protein of unknown function. mRNA #5 was detected in the liver hepatocytes of male and female GH transgenic mice and in the liver of female, but not of male, non-transgenic mice. mRNA #5 was not present in dwarf mice including the Ames dwarf, those that express a GH antagonist and those with the GH receptor and binding protein gene disrupted. These findings suggest that induction of mRNA #5 in the liver requires a continuous pattern of GH secretion and an intact GH-GH receptor-signaling complex. mRNA #5 levels in female non-transgenic mice were observed to vary with age implying that gender-specific age-dependent factor(s) may be involved in the induction of mRNA #5. The appearance of mRNA #5 in post-hepatectomized liver that coincides with the proliferative phase of liver regeneration suggests that it may be involved in hepatocyte proliferation. Together these data suggest that expression of cDNA #5 is liver-specific, sexually dimorphic, age-dependent, and may be involved in hepatocyte hyperplasia and liver enlargement.