The purpose of this study was to evaluate clinical, microbiological, and gingival crevicular fluid (GCF) profiles in periodontitis-resistant and periodontitis-susceptible subjects during 4 weeks of experimental gingivitis. Experimental groups of similar ages were defined as gingivitis controls (GC; n = 10) and history of rapidly progressive periodontitis (RPP; n = 10), respectively. Prior to baseline, all subjects achieved good plaque control (plaque index (P1I) approximately 0) and gingival health (gingival index (GI) = 0), and had probing depths < or = 4 mm on experimental teeth. For 4 weeks after baseline, oral hygiene around maxillary 2nd premolar and 1st molar teeth was inhibited by a plaque guard. The plaque guard was removed weekly for GCF sampling to determine interleukin (IL)-1 beta and prostaglandin (PG)E2 amounts by ELISAs. In addition, P1I, GI, probing depth, and gingival recession measurements were made. Subgingival plaque darkfield microscopy and DNA probe analysis also were performed. Results indicated that clinical signs of inflammation, microbiological patterns and GCF profiles progressed similarly in both groups. However, plaque accumulated more rapidly in the susceptible subjects. P1I in RPP at 4 weeks was 2.1 +/- 0.1 compared to 1.5 +/- 0.2 in GC, with an incidence of P1I > of 100% versus 50%, respectively (logistic regression; p < 0.0001). Hence, the clinical, microbiological and host factors selected for this study were unrelated to previous susceptibility to periodontitis when evaluated in the experimental gingivitis model. However, the increased rate of plaque accumulation, following thorough plaque removal, in RPP patients suggests a potential factor in disease recurrence in these susceptible subjects.