The establishment of a GH-regulated IGF-I network is essential for successful adaptation to postnatal life and the ratio of hepatic class 2: class 1 mRNA IGF-I levels may be positively regulated by GH status. The aim of this study was to investigate mechanisms accounting for these observations. Lambs were treated with GH either as an acute, single dose or longer term (8 days). 1) Total hepatic unspliced, pre-mRNA levels increased significantly after the single dose of GH but were attenuated after 8 days of GH treatment (P<0.01), exon 1- and 2-derived pre-mRNA levels displaying co-ordinate responses. 2) Surprisingly, changes in total spliced, mature mRNA levels did not reflect those for pre-mRNA, instead being augmented after 8 days' GH (P<0.01). 3) As expected, GH induced a differential increase in the ratio of mature class 2: class 1 IGF-I mRNA (P<0.001). Therefore if pre-mRNA levels can be assumed to reflect transcription rate, the GH-induced increase in hepatic class 2: class 1 mature mRNA levels must be predominantly via post-transcriptional mechanisms. 4) Significant increases in the ratio of class 2: class 1 mRNA were observed in polysomal versus total RNA preparations derived from GH treated but not control lambs, indicating an increased proportion of class 2 transcripts engaged in translation. Our data suggest that GH stabilizes mature class 2 transcripts or destabilizes mature class 1 transcripts and that class 2 mRNA may have a greater translational potential; sequence analysis indicates that class 2-derived IGF-I may be secreted more efficiently than class 1 peptide. We therefore suggest that the main function of hepatic class 2 IGF-I mRNA is twofold: an efficient 'monitor' of GH status by providing an efficient negative feedback response to increased circulating GH concentrations, and a coordinator of endocrine-regulated tissue growth.