Mass-directed isolation of the CH2Cl2/CH3OH extract from a marine sponge of the genus Pseudoceratina resulted in the purification of a new antimalarial bromotyrosine alkaloid, psammaplysin H (1), along with the previously isolated analogs psammaplysins G (2) and F (3). The structure of 1 was elucidated following 1D and 2D NMR, and MS data analysis. All compounds were tested in vitro against the 3D7 line of Plasmodium falciparum and mammalian cell lines (HEK293 and HepG2), with 1 having the most potent (IC50 0.41 mu M) and selective (> 97-fold) antimalarial activity. (C) 2010 Elsevier Ltd. All rights reserved.