Inducible cyclooxygenase-2 (COX-2) has been suggested to play a role in the processes of inflammation and carcinogenesis. Recent studies have shown the chemoprotective effects of kahweol and cafestol, which are coffee-specific diterpenes. This study investigated the effects of kahweol and cafestol on the expression of COX-2 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Kahweol and cafestol significantly suppressed the LPS-induced production of prostaglandin E(2), COX-2 protein and mRNA expression, and COX-2 promoter activity in a dose-dependent manner. Furthermore, kahweol blocked the LPS-induced activation of NF-kappaB by preventing IkappaB degradation and inhibiting IkappaB kinase activity. These results will provide new insights into the anti-inflammatory and anti-carcinogenic properties of kahweol and cafestol.