['To explore the contribution of an altered structure of sperm mitochondria to human asthenozoospermia.', 'A retrospective study.', "Andrology Clinic, University of L'Aquila.", 'Fifteen ejaculates with forward motility (FM) ≥ 50%, and 57 asthenozoospermic ejaculates (FM <50%, sperm vitality >50%), including 14 ejaculates with systematic genetic defects of tail principal piece, and 43 ejaculates with unexplained asthenozoospermia.', 'Fifty sections of tail middle piece (MP) were blindly analyzed by transmission electron microscopy in each ejaculate for normal mitochondrial membrane organization, after exclusion of tails with disrupted cell membranes.', 'Percentage of MPs with normal mitochondrial membranes (% normal MPs).', 'Percent normal MPs showed a strong correlation with forward motility. Variation of % normal MPs explained a 45% variation of sperm motility at multivariate linear regression analysis, confirming the strong association between the two parameters in a population including ejaculates with normal motility and with unexplained asthenozoospermia. Percent normal MPs was significantly reduced in severe unexplained asthenozoospermia (FM <10%; n = 16) compared with samples with normal motility (FM ≥ 50%; n = 15); 21% (10.5%-38%) and 68% (52%-73%), respectively.'] Is altered ultrastructure of mitochondrial membranes strongly associated with unexplained asthenozoospermia?