In a series of 50 consecutive biopsies of peroneus brevis muscle (PBm) taken from patients with ascertained or suspected polyneuropathy in the course of sural nerve biopsy, we found a high incidence (26%) of intramitochondrial paracrystalline inclusions (MPI). Five out of these 13 patients were also submitted to an additional biopsy of a proximal muscle, which in no case confirmed the finding of MPI. Six out of the 13 patients with MPI were affected by diseases with a presumably important ischemic component. The mean age of patients with MPI was quite elevated (60.7), and the difference in distribution of age between patients with and without MPI was statistically significant. No significant difference in histochemical changes was found between the group of MPI patients and a control group of age-matched patients without MPI, thus excluding that MPI in the PBm are specifically associated with other neurogenic or myopathic aspects. We conclude that aging and, probably, ischemia are largely responsible for the frequent presence of MPI in the PBm. In addition, factors intrinsic to the muscle itself, possibly related to morphological, physiological, or biochemical peculiarities, may also influence the development of MPI.