Nucleoside natural products are important chemical models for drug discovery and therapeutic intervention in human diseases including cancer, fungal infections, and viral infections related to human immunodeficiency viruses (HWs). Recent reviews by Isono1,2 list more than 200 known naturally occurring nucleoside antibiotics including several highly modified nucleosides isolated from marine invertebrates, such as sponges and algae.1-3 We now describe two novel cytotoxic nucleosides trachycladine A (9-(2'-C-methyl-5'-deoxy-β-D-ribofuranosyl)-2-chloroadenine, 1) and trachycladine B (9-(2'-C-methyl-5'-deoxy-β-D-ribofuranosyl)-2-hypoxanthine, 2) that occur in the sponge Trachycladus laevispirulifer Carter (Order Axinellida, Family Trachycladidae) from Exmouth Gulf, Western Australia. Both nucleosides possess an undescribed branched 5-deoxy-2-C-methyl sugar, and 1 is an analog of 2-chloro-2'-deoxyadenosine which has demonstrated remarkable clinical activity against hairy cell leukemia.4-6 Chloroadenosine analogs are rare in nature, having been found previously only in Streptomyces sp.7,8