Purpose: The purposes of this study were to investigate the periodontal status and susceptibility to periodontal disease progression of the teeth in contact with removable partial dentures (RPD) and to compare them with control teeth in mouths not restored with a partial denture, by means of both clinical parameters and interleukin (IL)-1beta levels in gingival crevicular fluid. Materials and Methods: Twenty-eight periodontally healthy patients were selected for the study; 14 of them were treated with mandibular Kennedy Class I RPDs, and the other 14 patients were not restored for control. Clinical periodontal measurements were assessed, and crevicular fluid samples were collected from both abutment and control teeth to determine IL-1beta levels, which were measured by enzyme-linked immunosorbent assay. These procedures were performed both at baseline and 9 months after the insertion of the dentures. Results: The wearing of RPDs resulted in statistically higher clinical scores and total IL-1beta levels compared to the baseline examination. In contrast, no statistically significant differences were found between baseline and 9-month examinations in the control group. Conclusion: RPDs are a risk factor for periodontal disease progression because of increased plaque accumulation associated with increased total IL-1beta levels and impaired clinical periodontal parameters.