Inadequate caloric intake inhibits longitudinal bone growth. This study was designed to investigate the mechanisms responsible for this suppression of growth plate function, focusing on the roles of systemic and local insulin-like growth factor 1 (IGF-1). Five week-old male rabbits were fasted for 48 h. Fasting significantly decreased proximal tibial growth velocity and growth plate width (both proliferative and hypertrophic zones). During the fast, systemic IGF-1 production was down-regulated. Serum IGF-1 levels and hepatic IGF-1 messenger RNA (mRNA) levels decreased despite increased GH levels. Serum levels of GH binding protein (a circulating fragment of the GH receptor) and hepatic GH receptor mRNA levels were not significantly changed. In contrast, the local, growth plate IGF-1 system appeared to be up-regulated. Growth plate GH receptor mRNA and IGF-1 mRNA levels were both increased during fasting. We conclude that, in the rabbit, fasting induces a rapid depletion of growth plate chondrocytes and inhibition of longitudinal bone growth. These effects appear to be mediated by systemic endocrine mechanisms; circulating IGF-1 levels are diminished because of hepatic resistance to GH. In contrast, the local, paracrine IGF-1 system in growth plate does not appear to contribute to the growth inhibition but instead appears to be up-regulated by fasting.