The aim of the present investigation was to study the local nature of human periodontal disease by assessing the microbiota and the composition of the tissue lesions at sites with progressive attachment loss in periodontitis susceptible subjects. 300 subjects with periodontal disease were monitored for 2 years without treatment. 8 subjects lost > 2 mm of attachment at > or = 3 sites during both the first and the second 12 month interval. These 8 subjects (progressive disease group; PD) were recalled for a microbiological and histopathological examination. A group of age- and sex-matched subjects were identified who during the 2 years of monitoring exhibited gingivitis and deep pockets, but no further attachment loss. This group of 11 subjects (non-progressive disease group; NPD) served as controls. From the 8 active disease subjects, > or = 1 interproximal site which had displayed disease activity (progressive disease active; PDA) and > or = 1 contralateral site without disease progression (progressive disease inactive; PDI) were sampled. From the 11 control subjects, 1 site/subject was sampled (NPD). The total number of viable micro-organisms (TVC) in the subgingival microbiota was estimated and a series of bacterial species were identified and enumerated. The gingival tissue of the sampling site was excised and the soft tissue prepared for morphometrical and immunohistochemical analyses. No differences were observed in the subgingival microbiota of the sample sites in the subjects who exhibited disease progression (PD) when compared with the subjects with periodontally diseased but stable conditions (NPD).(ABSTRACT TRUNCATED AT 250 WORDS)