BACKGROUND Patients who smoke are at increased risk for chronic periodontitis (CP). Also, CP patients who smoke exhibit significantly less reduction of probing depths and gains in clinical attachment compared to non-smokers following periodontal therapy. Several studies suggest that the effects of smoking on the host response may be paramount in regulating the basal systemic inflammatory status and therapeutic outcomes in this cohort. Growth factors, specifically transforming growth factor beta1 (TGF-beta1), are critical in regulating the wound healing response by controlling cell division, differentiation, and motility. The hypothesis to be tested was that gingival crevicular fluid (GCF) TGF-beta1 production was altered in smokers compared to non-smokers with CP. METHODS GCF was collected from smokers and non-smokers with CP, both at baseline and 1 to 2 weeks after initial therapy. GCF volume was determined using an electronic device and TGF-beta1 concentration was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Smokers exhibited a higher mean concentration of GCF TGF-beta1 at baseline compared to non-smokers (P = 0.03). After initial therapy, smokers exhibited significantly less reduction in mean GCF volume compared to non-smokers (P = 0.04). CONCLUSIONS Augmented constitutive production of GCF TGF-beta1 in smokers may explain the clinical appearance of fibrotic gingival tissue exhibited by this patient cohort. A diminished reduction in GCF volume in smokers following root instrumentation suggests a chronic inflammatory status in conjunction with an ineffective host response. These findings support the concept that smokers with CP display an altered local inflammatory response after initial therapy, perhaps symptomatic of colonization by residual periodontal pathogens.