In this study we tested the hypothesis that, compared to young adult rats, senescent rats have a reduced ability to respond to muscle unloading. Unloading of the muscles was induced by hindlimb suspension (HS) of young adult and senescent rats for 21 days. Plantaris muscles from young adult rats had significantly higher levels of myogenin mRNA and protein (890% and 314%, respectively, P<0.05) than plantaris muscles from senescent rats and also a higher MyoD mRNA level (280%, P<0.05), but ageing did not increase MyoD protein levels. Although HS did not increase plantaris mRNA or protein levels of myogenin or MyoD in senescent rats (P = 0.22), myogenin mRNA and protein levels increased by 850% and 580% respectively, and MyoD mRNA and protein levels by 235% and 1600%, respectively in young adult rats (P < 0.05). Soleus muscles from senescent rats had 150% and 85% greater myogenin and MyoD mRNA levels, respectively (P<0.05), than soleus muscles from young adult rats, whereas protein levels of myogenin were similar (P>0.05) and MyoD protein levels were 60% lower in the muscle of senescent rats (P<0.05). In young rats, soleus muscle mRNA levels of myogenin and MyoD were not altered by HS but myogenin protein levels decreased by 57% (P<0.05) whereas MyoD protein levels increased by 187% (P<0.05). In senescent rats, HS decreased soleus muscle myogenin mRNA and protein levels by 42% and 26% respectively (P<0.05), but MyoD protein and mRNA levels were not changed. MRF4 levels were not affected by ageing in either muscle. These data suggest that ageing reduces the ability of fast muscles to increase myogenin protein levels, and prevents both fast and slow muscle from increasing MyoD protein levels during muscle unloading.