The purpose of this study was to investigate whether the polymorphisms in the control region of mitochondrial DNA (mtDNA) related to individual difference in the endurance capacity or trainability. Fifty-five sedentary males participated in this study and were submitted to an 8-week endurance training program. The VO(2 max) was determined before and after training. Total DNA was extracted from the blood, and the sequence of the mtDNA control region was determined. The polymorphism in the mtDNA control region was decided based on the "Cambridge sequence." In 29 of the 55 subjects, vastus lateralis muscle biopsy samples were taken at rest before and after the training program. MtDNA content and CS (citrate synthase) activity in skeletal muscle was measured as the phenotype of the polymorphisms in the mtDNA control region. The VO(2 max) increased to 48.2 +/- 6.3 ml/min/kg from 42.1 +/- 6.0 as a result of the 8-week training (p < 0.05). The numbers of polymorphisms in determined 1,122 bp were 11.1 +/- 2.9 variable sites per person, and the total numbers of polymorphisms were 125 variable sites. The subjects were classified into two groups at each variable site, the Cambridge sequence (Cam) group and the non-Cambridge sequence (non-Cam) group. There were significant differences in pre-VO(2 max) between the two groups at each mtDNA nucleotide positions 16298, 16325, and 199, and in % Delta VO(2 max) at 16223 and 16362. Twenty-nine subjects who underwent the biopsy revealed significant differences in pre-CS activity at 194 and pre-mtDNA content at 514. Also, significant differences were found in the change rate of VO(2 max )and CS activity as a result of training between the two groups at 16519. In conclusion, it suggested that mtDNA polymorphisms in the control region might result in individual differences in endurance capacity or trainability.