OBJECTIVE Local neuropeptide release has a critical role in the initiation and progression of an inflammatory response. This study investigated the effects of different restorative materials on periodontium in this regard, by evaluating their neuropeptide-producing effects on gingival crevicular fluid (GCF). METHODS The study included 14 patients suitable for metal-ceramic, composite and amalgam restorations. Four weeks after periodontal therapy, the restorations were performed. Study groups were constituted regarding the tooth/restoration surfaces contacting gingiva in each patient: 1 ceramic surface of a metal-ceramic crown (ceramic group), its opposite metal surface (metal group), 1 composite surface (composite group), its opposite enamel surface (opposite-composite group), 1 amalgam surface (amalgam group), its opposite enamel surface (opposite-amalgam group) and 1 nonrestored enamel surface (enamel group). Four weeks after dental restorations, clinical data and GCF were obtained from the group sites. Clinical data, GCF volume and its proinflammatory cytokine profile were utilized to evaluate the periodontal health. GCF levels of substance P (SP), neurokinin A (NKA) and calcitonin-gene related peptide (CGRP) were determined by ELISA for revealing the neuropeptide levels. RESULTS GCF volume was found to increase in all groups compared with the enamel group (p<0.05). SP and NKA levels were higher in the ceramic, composite and amalgam groups than those in the enamel group (p<0.05). SP and NKA levels were also higher in the composite and amalgam groups than those in the opposite-composite/amalgam groups (p<0.05). CONCLUSIONS These results suggest that ceramic, composite and amalgam materials may uniquely trigger local neuropeptide release in periodontium.