Huntington's disease is generally considered to be a late-onset neurodegenerative disorder, which follows a protracted course of deteriorating motor control and cognitive impairment. However, in a minority of cases, the onset of symptoms occurs early in life. A preponderance of the juvenile-onset HD victims have inherited the genetic defect from their fathers. This variation in age of onset, based on the sex of the affected parent, has suggested that maternally inherited genes may influence expression of the disorder. We describe a portion of a large Venezuelan HD pedigree in which both the mother and father of three juvenile-onset HD patients share a common maternal lineage. Scanning of mtDNA from members of this family with 43 restriction endonucleases failed to reveal any differences in the mitochondrial genotype that could account for the difference in age of onset between the affected father and his progeny. Members of a related family with an affected father but no juvenile-onset progeny also appeared to share the same mitochondrial genotype. In addition, the mitochondrial gene products from lymphoblast cell lines of these family members were analyzed on polyacrylamide gels after incubation of cells with [35S]methionine, but no detectable alterations were seen. Taken together, these data suggest that the maternally inherited mitochondrial genome does not play a crucial role in determining in age of onset in HD.