Ghrelin activates GH release and is implicated in growth and metabolic regulation. The regulation of its biosynthesis has not been well studied. The current investigation was designed to examine some of the factors that may influence ghrelin gene expression in the stomach. Thus, in C57BL/6 mice, ghrelin mRNA was detectable by Northern blots throughout the age groups studied, but the levels changed markedly over time. Levels were low at E18.5 and increased rapidly after birth to 6-fold at P14 before peaking to 8-fold at P21. The levels then exhibited a gradual decline at P60 (75% of the peak level) and at 6 months (67%) and a drastic decrease as the animals aged to 19 months (only 5%). Furthermore, sexual dimorphic gene expression, the effect of liver-derived IGF-I deficiency, as well as ghrelin secretion were studied. Our results support a role of ghrelin in growth/metabolism in juvenile and young adult mice of both sexes and in sexually dimorphic regulation of GH secretion in aged mice.