A study of a consanguineous family with a high prevalence of localized juvenile periodontitis (LJP) and generalized prepubertal periodontitis (GPP) was done over a 7-and-a-half year period. The parents had adult periodontitis, while 2 daughters, aged 13 and 15, had LJP. Furthermore, 2 other daughters, ages 14 and 10, and a son, aged 9, were affected by GPP. Two remaining siblings were not affected. Clinical and radiographic examinations on all family members were done, and chemotaxis for blood neutrophils was assessed. Laboratory tests, immunological examinations, and evaluation for neutrophil functions were done on the GPP patients. Microbiological cultures were performed on 2 of the GPP patients, as well as in the mother. The mother, the 2 LJP patients, and 1 of the unaffected siblings had depressed PMN chemotaxis. The other family members, including the 3 GPP patients, had normal PMN chemotaxis. GPP patients did not have any systemic disease, and evidence of major defects in the immunological functions was not detected. LJP patients were successfully treated with root planing, subgingival curettage, and tetracycline therapy. Intensive periodontal therapy, combined with systemic administration of antibiotics, was not effective in halting periodontal tissue destruction in the 3 GPP patients. Results indicate that the underlying cause of GPP is not always related to leukocyte dysfunction. Since Actinobacillus actinomycetemcomitans was the most frequent pathogen found in subgingival microflora of 2 of the GPP patients, it is assumed that it may play a key role in the etiology of GPP.