Cnidarian-dinoflagellate symbioses are mutualistic endosymbioses in which the algae live in the cells of host organisms, providing nutrients to the host while the host supplies a protective environment or living expenses to the algae. The molecules involved in the initiation, establishment, and maintenance of these endosymbioses remain largely unexplored. Suppression subtractive hybridization (SSH) was applied to identify genes in the sea anemone, Aiptasia pulchella Carlgren 1943, that are differentially expressed in specimens with or without symbionts. Eleven candidate transcripts were isolated, seven of which were confirmed unique and differentially expressed. Two genes were further analyzed to complete the full-length cDNAs. Phylogenetic analysis suggested the full-length 1A6 cDNA, which is upregulated in anemones containing the symbiont, codes for the sea anemone Niemann-Pick type C2 homologue that is involved in lysosomal cholesterol transport. The predicted secondary structure and folding analysis of the deduced amino acid of 2C7 cDNA, which is upregulated in anemones without the symbiont, suggested that Mlc1p, a calmodulin-like myosin light chain from the budding yeast Saccharomyces cerevisiae, is closely associated. Using SSH, we demonstrated that A. pulchella differentially expresses transcripts under symbiotic or aposymbiotic conditions.