Papillon-Lefèvre Syndrome (PLS) is a rare disease associated with the early onset of periodontal breakdown in deciduous and permanent dentition. The etiology of the destruction has not been completely clarified. Two female patients (ages 4 and 7 years) with severe destruction of the periodontal structures were examined. Except for palmar and plantar hyperkeratosis, dermatologic examination revealed no other medical disorders. On immunological analysis, measurement of serum antibody titers to 7 periodontopathic bacteria including Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans was performed by enzyme-linked immunosorbent assay (ELISA). Further immunoblot analysis of A. actinomycetemcomitans and microbial culture of samples collected from deep periodontal pockets and mouthrinse solution were performed. The serum of the two patients showed high IgG titer against A. actinomycetemcomitans. Immunoblot results of the two patients against sonicated extract of A. actinomycetemcomitans Y4 strain exhibited a similar pattern. The band pattern differed from that observed in other forms of early onset periodontitis patients or periodontally healthy subjects. Moreover, A. actinomycetemcomitans colonies were cultured in high percentages from the pocket samples. Antibiotic therapy was instituted in addition to conventional periodontal therapy. In the younger patient, all deciduous teeth were extracted as part of the treatment and A. actinomycetemcomitans was no longer detected. All four permanent first molars and 8 permanent incisors subsequently erupted with healthy periodontium. However, the older patient did not improve after periodontal and antibiotic (minocycline and erythromycin) treatments and A. actinomycetemcomitans was consistently detected. Ofloxacin medication finally eliminated A. actinomycetemcomitans from the periodontal pockets. This antibiotic was also associated with reduced gingival inflammation and probing depth.(ABSTRACT TRUNCATED AT 250 WORDS)