The actions of the insulin-like growth factors (IGF-I and ICF-II) which are essential components of skeletal muscle growth are mediated via their receptors and modulated by six binding proteins (IGFBPs). We studied IGFBP transcripts in C2C12 cell cultures and in adult control and denervated gastrocnemius muscle. IGFBP-2, -4, -5, and -6 were detected in C2C12 cells. IGFBP-6 mRNA levels remained unchanged, IGFBP-2 levels decreased and IGFBP-4 and -5 increased over 1, 5, and 9 days after serum reduction. In a range of adult muscles studied, IGFBP-4 mRNA levels were similar, IGFBP-5 was present at different levels in slow and fast muscles and IGFBP-6 had the lowest expression in the tibialis anterior. Denervation resulted in dramatic up-regulation of IGFBP-4 and -5 transcripts but there was no change in IGFBP-6. These results suggest that either lack of neural input and/or mechanical loading, both of which contribute to muscle atrophy, affect IGFBP expression.