The present study was undertaken to investigate the e ffects of some phenol-related compounds on the expression of lipopolysaccharide LPS -stimulated cyclooxygenase-2 COX-2 and activation of nuclear factor kappa-B NF- B in the murine macrophage-like cell line, RAW264.7. LPS induced the expression of COX-2 mRNA and protein at 3 and 6 hours after the start of treatment, respectively. Next, the effects of p -cresol, thymol, 2,4-di- tert -butylphenol DTBP , 2,2 -dihydroxy- 5,5 -dimethyl biphenyl DDBP, a cresol dimer and 3,3,5,5-tetra- tert -butyl- 1,1-biphenyl-2,2-diol TTBBD, a DTBP dimer on LPS-induced COX-2 expression, were investigated. The LPS-indu ced expression of COX-2 was inhibited slightly by p -cresol and thymol at 10 M, whereas it was inhibited more strongly by DDBP and TTBBD than by the monomeric compounds. DTBP was not inhibitory. When the effects of these compounds on activation of the transcription factor NF- B were investigated, DDBP and TTBBD mark- edly inhibited LPS-stimulated phosphorylation and proteolysis of I B- . These phenolic compounds also strongly inhibited the LPS-stimulated binding of NF- B components p65, p50 and p52 to the consensus sequences. These observations suggest that DDBP and TTBBD may act as inhibitors of LPS-induced COX-2 expression via suppression of NF- B activation by inhibiting the phosphorylation of I B- , and that phenolic dimer compounds such as DDBP and TTBBD may be effective therapeutic agentsagainst chronic inflammatory diseases involving COX-2.