Recent studies have reported that sealers may alter the secretion of specific cytokines from THP1 monocytic cells in vitro. In this study, a cytokine array was used to determine if endodontic sealers changed secretion of 42 cytokines. White mineral trioxide aggregate (WMTA), MTA preparation (CS), AH-Plus (AHP), and Pulp Canal Sealer (PCS) were mixed, allowed to set for 72 h, then "aged" in buffered-saline for 12 weeks. Aged specimens were placed in direct contact with THP1 for 72 h and their cytotoxicity (MTT assay) was assessed. Materials that were not severely toxic were then exposed to THP1 with or without lipolysaccharide (LPS), and the culture medium was assayed for cytokine secretion. Secretion of cytokines was quantified using infrared scanning (Odyssey(®)); replicate pairs were averaged. PCS severely suppressed MTT activity and was not assessed for its influence on cytokine secretion. WMTA, CS, and AHP induced a broad-based increase in cytokine secretion (>20% vs. Teflon controls), but AHP induced the greatest increase (>100% in 17 of 42 cytokines). The effects of the sealers on LPS-activated THP1 were biphasic, with some increases and decreases cytokine secretion of >20%, but few larger effects. This work shows endodontic sealers may alter the secretion of a broad cross section of cytokines from monocytic cells.