An extract of a marine sponge, Hippospongia sp., collected in Palau has inhibitory activity against colony formation by Chinese hamster V79 cells. Bioassay-guided isolation gave eleven sesquiterpene quinones. Compounds 1–8 inhibited colony formation by V79 cells with EC50 values between 0.6 and 2.8 lmol L–1. Their effects on the production of an inflammatory cytokine, IL-8, in tetradecanoyl phorbol acetate (PMA)-stimulated HL-60 cells were also investigated, because IL-8 production is sometimes correlated with inhibition of cell growth. Ilimaquinone (1) and its 5 epimer (2) had similar activity against V79 cells (EC50 = 2.8 and 2.3 lmol L–1, respectively) but did not modulate IL-8 production even at 10 lmol L–1. Smenospongidine (3) and its 5 epimer (4), smenospongiarine (5) and its 5 epimer (6), and smenospongine (7) and its 5-epimer (8), at 10 lmol L–1, promoted IL-8 production. Compounds 3, 5, and 7 had slightly stronger activity against V79 cells (EC50 = 0.6, 1.7, and 0.8 lmol L–1, respectively) than the corresponding 5 epimers 4, 6, and 8 (EC50 = 0.8, 2.3, and 2.0 lmol L–1, respectively). A similar structure–activity relationship was observed for promotion of IL-8 production. This is the first report of modulation of IL-8 production by these sesquiterpene quinones.