Early-onset periodontitis (EOP) refers to a group of severe periodontal diseases with age of onset near puberty that are characterized by rapid destruction of the tissues supporting the teeth in otherwise healthy individuals. Mixed model segregation analyses of 100 families, ascertained through 104 probands with EOP, were carried out to test major locus and multifactorial hypotheses for the etiology of EOP. Heterogeneity tests were used to compare the parameter estimates and conclusions obtained in Black families from those from non-Black families. The data in these families confirmed that the often-reported female preponderance of EOP appears to be an ascertainment bias. The segregation analysis results were consistent with an autosomal major locus being sufficient to explain the family patterns of EOP in the entire dataset, and also in both the Black and non-Black subsets. A dominant mode of transmission was most likely, with penetrance of about 70%. Although the etiologic conclusions were the same for Black and non-Black families, there was significant heterogeneity in parameter estimates. In particular the Black allele frequency was 0.016 versus the non-Black frequency of 0.001.