Three novel halogenated metabolites [1-3], derived from tyrosine, have been isolated from the Caribbean sponge Iotrochota birotulata, and their structures determined by spectroscopic means. Brominated tyrosine-derived metabolites such as 1 have previously been considered to be characteristic of species in the order Verongida, to which I. birotulata does not belong. The frequent occurrence of halogenated, and particularly brominated, metabolites is a unique feature of marine natural product chemistry. They are not uniformly distributed among the marine plant and invertebrate taxa, and are most commonly found in red algae and sponges. Even in this latter phylum they are present in a relatively small number of species, and are mainly associated with horny sponges, which are distributed in the three orders Dictyoceratida, Dendroceratida, and Verongida. In particular, Verongida are characterized by their ability to synthesize bromotyrosine derivatives, which seem to be peculiar to these sponges, and have been suggested as chemical markers for taxonomic studies (1). In our continuing studies on the secondary metabolites from marine invertebrates, we have now isolated three new, quite unusual compounds [1-3] from Iotrochota birotulata (Higgin, 1877) (Esperiopsidae; Poecilosclerida). Iotrochota birotulata is a tropical marine sponge which forms ramose, bushy aggregates of thick branches (1.5 cm across) with a conulose surface; the sponge is purplish black to black in color, and occasionally green in life. It gives off a dark exudate when squeezed. The sponge is widely distributed, coming from reefs, but also from deeper waters, and even from hidden positions in shallow bays. Its distribution ranges all over the Caribbean, although the conspecificity of Indo-Pacific specimens requires verification. In 1979, from a sample of I. birotulata collected along the coasts of Miami, Florida, Baden and Corbett (2) isolated a peroxidase, which showed an activity characteristic of halogenating enzymes. The haloperoxidases are known to play a key role in the biosynthesis of the halogenated naturally occurring compounds (3). However, until now no halometabolites have been isolated from this sponge. Compounds 1-3 appear to be interesting in several ways. Each of these mixed-biogenesis metabolites contains a halogenated partial structure, very probably arising from tyrosine, which for compound 1 closely resembles bromo-compounds from sponges classified in the order Verongida. It is noteworthy that this brominated metabolite derived from tyrosine has been isolated in this study in a species taxonomically far removed from Verongida; to our knowledge, I. birotulata is the first sponge that elaborates such metabolites not belonging to the order Verongida. The existence of a mevalonate-derived moiety in the molecule is also very unusual for a halogenated derivative of tyrosine. The presence of iodine atoms in compounds 2 and 3 is another interesting issue. Iodo-compounds are relatively rare in marine chemistry and particularly in sponges, even if all known haloperoxidases are effective in oxidizing iodide (3). The biosynthesis of iodinated metabolites seems to be related to the capability of organisms to concentrate iodide from sea water, rather than to the presence of a specific peroxidase; most of iodo-metabolites have been isolated from red algae, which are known to contain iodine concentrations as high as 0.5% of wet wt. Interestingly, Kaestner reported that significant amounts of iodine (0.12-1.21%), together with comparable quantities of bromine (0.16-2.66%), are present in the spicule tracts of I. birotulata, cemented with variable amounts of spongin (4). This further confirms the relationship between the presence of iodo-metabolites and high concentrations of iodine in the sponge tissues.