An extract of Melastoma dodecandrum LOUR. with 80% aqueous acetone (MDL) inhibited nitric oxide (NO) production by a murine macrophage-like cell line, RAW264.7, activated with lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma). On further fractionation of the extract, the majority of the inhibitory activity was recovered in the 50% methanol extracts, which contained hydrolyzable tannins. Among the latter, casuarinin, casuarictin, pedunclagin and nobotannin B exhibited strong inhibitory activities toward NO production, with ID50 values between 2.0 and 5.1 microM. Both MDL and the purified tannins significantly reduced the induction of the inducible nitric oxide synthase (iNOS) protein in the course of macrophage activation with LPS and IFN-gamma. In addition, the NO production by macrophages preactivated with LPS and IFN-gamma for 16 h was also inhibited by these tannins, with IC50 values around 30-130 microM, but not by MDL. These results suggest that MDL has the pharmacological ability to suppress NO production by activated macrophages and that the hydrolyzable tannins have major inhibitory activities.