Fast skeletal muscle fiber type II is highly specialized to perform movements of high velocity and exert high forces. Our investigation aims to analyze which physiological stimuli and signalling pathways stimulate MHCIId/x expression in skeletal muscle cells in culture. Cells were electrostimulated or exposed to passive mechanical forces in culture for several days. Passive mechanical forces led to a strong stimulation of expression of MHCIId/x on mRNA and protein levels as well as induction of IGF-1 mRNA expression, while slow MHCI expression was not affected. Chronic electrostimulation with different patterns showed that slow MHCI expression was highly inducible by certain patterns but this induction was suppressed when passive forces were applied simultaneously. The induction of MHCIId/x expression was strongly repressed by pharmacological p38 MAPK inhibition. Additionally, electrostimulation led to p38 MAPK inhibition with concomitant MHCIId/x repression. Further experiments using calcium ionophore treatment revealed that p38 MAPK inhibition is calcium dependant. It appears that mechanical forces mainly support the growth of fast muscle fibre type through a combination of induction of a p38 MAPK dependent MHCIId/x transcription and upregulation of IGF-1 transcription, while the slow fibre type (MHCI) is essentially governed by contractile activity-dependent calcium signalling.