The rat insulin-like-growth-factor-(IGF)-II gene is expressed at high levels during embryonic and fetal life and at low levels in adult animals. To study the regulation of IGF-II gene expression, we analyzed the synthesis and localization of the IGF-II transcripts in cultured rat liver cells either expressing (BRL3A cells) or not expressing (BRL30E and FAO cells) the IGF-II mRNA. The IGF-II gene is transcribed at a similar rate in expressing and non-expressing cells, whereas its nuclear and cytoplasmic RNA levels are diversely distributed in the cells. IGF-II RNA is more abundant in the cytoplasmic than in the nuclear RNA fraction of BRL3A cells and is present in the nucleus but not in the cytoplasm of the FAO cells. However, both precursor and mature IGF-II nuclear RNA levels are reduced in FAO cells. Our data indicate that the IGF-II gene expression is regulated by mechanisms affecting the subcellular distribution and the abundance of the transcripts.