Twenty-five acridone alkaloids from Citrus plants were examined for their inhibitory effects on Epstein-Barr virus activation by a short-term in vitro assay. 5-Hydroxynoracronycine (20) and acrimarine-F (25) showed remarkable inhibitory effects.We have been studying the constituents of Citrus plants and have isolated many new and known acridone alkaloids (1). With the general acceptance of the two-stage carcinogenesis (initiation-promotion) theory, a promising method of chemoprevention of cancer has been regarded to be the inhibition of tumor promotion (2), and many studies involving drugs from natural sources have been reported (3). In this paper, we report on the inhibitory effects of these acridone alkaloids on Epstein-Barr virus activation. Although the cytotoxicity and mutagenesis of acridone alkaloids have been reported (4), this is the first report on their inhibitory effects on EBV-EA for anti-tumor promoting activity.Twenty-five acridone alkaloids 1—25 were tested and their inhibitory effects on activation and viabilities of Raji cells are shown in Table 1. All the test compounds showed weak cytotoxicity on Raji cells even at high concentration (1 x iO mol ratio). Among the compounds, 5-hydroxynoracronycine (20) and acrimarine-F (25) showed significant inhibitory effects (100% inhibition of activation at 1 x iO mol ratio/TPA, and 12—33% inhibition of activation even at 1 x 10 mol ratio/TPA) on EBV-EA activation. Citrusinine-lI (5), piimmeline (10), and prenylcitpressine (16) exhibited significant activities at I x iO mol ratio/TPA. Natsucitrine-I (3) and yukomine (14) showed remarkable inhibitory effects even at 1 x 10 mol ratio/TPA (10 and 17% inhibitions, respectively). In the series of acrimarines (22— 24), which are composed of acridone alkaloid and coumarin, acrimarine-F (25) and -B (23) with the 2-substituted structure, exhibited higher inhibitory activity than acrimarine-D (24) with the 4-substituted structure. These results suggested that 5-hydroxynoracronycine (20) and acrimarine-F (25) may be valuable anti-tumor promotors. Initiation-promotion tests of 20 and 25 in vivo are now in progress.