Oral gram-negative bacteria, including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Capnocytophaga sputigena, Provotella intermedius, Provotella melaninogenicus, have been associated with destructive periodontal infection. An ultrasensitive antibacterial assay was applied to determine the sensitivity of a battery of oral gram-negative bacteria to the bactericidal effects of the isolated human neutrophil defensins (HNP) and two kinds of rabbit defensins NP1 and NP2. All species tested were killed by HNP, NP1 and NP2 except that porphyromonas gingivalis was resistant to HNP. However, there was strain-to-strain variation in sensitivity. It was concluded that the oral gram-negative bacteria were sensitive to the cidal mechanism involved in defensinmediated bacterial killing.