It is now widely accepted that canonical Wnt signalling is essential for the formation of skeletal muscle during embryonic development (Münsterberg et al., 1995); yet far less is known about the role of this pathway in adult muscle. Mature skeletal muscle fibres are surrounded by a population of resident stem cells termed ‘satellite cells’ which are responsible for muscle repair and regeneration following exercise induced damage or injury. Recent research suggests that satellite cells are of embryonic origin which raises the possibility that these cells may be responsive to myogenic cues observed in the developing somite, such as Wnt proteins (Gros et al., 2005). Using primary human muscle cell culture as an in vitro model of human skeletal muscle regeneration and growth, the aim of the present study was to investigate whether the canonical Wnt signalling cascade was active and could be manipulated in these cells. Human satellite cells (myoblasts) were isolated from biopsy samples of the vastus lateralis of healthy young (23 ± 3.46 years) male volunteers (n = 3) following administration of a local anthestatic (2% lignocaine). Subsequent cultures were pre-plated to reduced fibroblast contamination and myogenic purity was assessed via desmin immunoreactivity (74-91% desmin+ve). Canonical Wnt signalling requires the nuclear import of dephosphorylated (active) β-catenin (Ser37 or Thr41) in order to activate Wnt target genes; thus the expression of this protein was measured by Western blotting. In proliferating myoblasts, dephosphorylated β-catenin was elevated in response to recombinant human Wnt-3A administration (200 ng/ml) at all time points studied when compared to untreated control cells; mean fold increases were 1.53 ± 0.25, 1.33 ± 0.14, 1.38 ± 0.06, 1.57 ± 0.47, 1.59 ± 0.29 at 1, 2, 4, 8 & 16 hours respectively; P <0.05). In addition, qPCR analysis revealed a significant increase in Axin-2 mRNA transcripts following Wnt-3A treatment at all time points except 1 hour (P <0.05). Mean fold increases in Axin-2 mRNA in Wnt treated cells compared to controls cells were: 2.17 ± 1.46, 5.94 ± 4.22, 8.72 ± 1.64, 8.45 ± 0.56 & 7.17 ± 1.24 at 1, 2, 4, 8 & 16 hours respectively. Axin-2 protein forms part of a multi-unit destruction complex which marks β-catenin for degradation in the absence of canonical Wnt ligands; thus the observed upregualtion of Axin-2 transcripts may represent a negative feedback loop reported for Wnt signalling in other animal cell types (Jho et al., 2002). Immunocytochemical analysis of β-catenin confirmed its cytoplasmic and nuclear expression in proliferating myoblasts. In conclusion this study has revealed an operative and perturbable canonical Wnt signalling pathway in primary human myoblasts.