The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor co-activator (PGC)-1 is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1knock-out (KO) and littermate wild-type (WT) mice performed a single treadmill running exercise bout. Soleus and white gastrocnemius (WG) were obtained immediately, 2h or 6h after exercise. Another group of PGC-1-KO and WT mice performed 5 weeks exercise training. Soleus, WG and quadriceps were obtained ~37 hours after the last training session. Resting muscles of the PGC-1-KO mice had lower (~ 20%) cytochrome c (cyt c), cytochrome oxidase (COX)I and aminolevulinate synthase (ALAS)1 mRNA and protein levels than WT, but similar levels of AMP activated protein kinase (AMPK)1, AMPK2 and hexokinase (HK) II compared with WT mice. A single exercise bout increased phosphorylation of AMPK and acetyl-CoA carboxylase- and the level of HKII mRNA similarly in KO and WT. In contrast cyt c mRNA in soleus was up regulated in WT muscles only. Exercise training increased cyt c, COXI, ALAS1 and HKII mRNA and protein levels equally in WT and KO animals, but cyt c, COXI and ALAS1 expression remained ~20% lower in KO animals. In conclusion, lack of PGC-1 reduced resting expression of cyt c, COXI and ALAS1 and exercise-induced cyt c mRNA expression. However PGC-1 is not mandatory for training-induced increases in ALAS1, COXI and cyt c expression showing that other factors than PGC-1 can exert these adaptations.