The mitochondrial volume densities (Vmit) of the different fiber types (type 1, type 2A, type 2B) were estimated in bilaterally obtained biopsies from 22 patients with unilateral intermittent claudication. These data, which were obtained from structurally intact fibers, were compared with clinical data from the same subject. In both the asymptomatic and symptomatic legs, Vmit 1 greater than Vmit 2A greater than Vmit 2B. Furthermore, Vmit 1 covariated with Vmit 2A and Vmit 2A with Vmit 2B in the asymptomatic legs (as in healthy subjects) but not in the symptomatic legs. Vmit 2 (mainly Vmit 2A) covariated with the age of the subjects in both legs. Vmit Tot was higher in the symptomatic legs than in the asymptomatic legs. This was mainly due to increase in the oxidative fibers, type 1 and type 2A. Usually, Vmit in the asymptomatic legs covariated significantly with the results of the functional tests (initial pain and maximum walking tolerance), while only Vmit 2A in the symptomatic legs showed such a correlation. However, the difference between the two legs concerning Vmit 1 was also correlated to the walking tolerance. Patients with high stenosis or occlusion showed higher Vmit Tot than did those with low obstacles. The results conclusively show that a fiber type-specific adaptation to ischemia occurs through an increase of mitochondrial content of oxidative fibers, which suggests that hypoxia may influence the control of synthesis or degradation of mitochondrial proteins.