The goal of this study was to provide new data regarding levels of inflammatory and growth factor mediators and bacterial pathogens associated with failing implants, as compared to healthy implants. Twenty-one patients with failing implant sites (group 1) and 8 patients with only healthy implants (group 2) were included. Fifteen of the 21 failing implant patients (group 1) also presented with at least one stable nondiseased implant. Plaque samples were examined, using DNA oligonucleotide probes for 40 different microbes. Gingival crevicular fluid samples were collected for the analyses of catabolic bone resorbing agonists prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and IL-6 and anabolic bone-forming growth factors transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF). Although positive trends were noted, there were no significant differences in any of the microbial, inflammatory, or growth factors mediators comparing failing to stable implants in group 1. This study found greater detection frequencies of P. nigrescens, P. micros, F. nucleatum ss vincentii, and F. nucleatum ss nucleatum, as well as significant elevations in GCF levels of PGE2, IL-1 beta, and PDGF in mouths with failing implant sites as compared to mouths with healthy control implants. Risk appears to be primarily at a patient level and secondarily at a site or implant level from a clinical, microbial (P. micros and P. nigrescens), and biochemical (PGE2 and IL-1 beta) perspective. Furthermore, the counts of P. nigrescens and P. micros were found to correlate with concentrations of PGE2 at a site level.