This study investigated mechanisms regulating hepatic insulin-like growth factor (IGF)-I class 1 and 2 mRNA levels. Lambs were treated with growth hormone (GH) either as an acute, single dose or over a longer term. Total hepatic unspliced, pre-mRNA levels increased after the single dose of GH but were attenuated after 8 days of GH, with exon 1- and 2-derived pre-mRNA levels displaying coordinate responses. Surprisingly, changes in total spliced, mature mRNA levels did not reflect those for pre-mRNA, instead being augmented after 8 days of GH. GH also induced a differential increase in the ratio of mature class 2-to-class 1 IGF-I mRNA; therefore, this must be predominantly via posttranscriptional mechanisms. Increases in the ratio of class 2-to-class 1 mRNA were observed in polysomal vs. total RNA preparations derived from GH-treated but not control lambs, indicating an increased proportion of class 2 transcripts engaged in translation. Our findings indicate that GH may stabilize mature class 2 transcripts or destabilize mature class 1 transcripts and that class 2 mRNA may have a greater translational potential. The following two main functions of hepatic class 2 IGF-I mRNA are suggested: an efficient “monitor” of GH status via providing a rapid negative feedback mechanism and a coordinator of endocrine-regulated tissue growth.