Three new bis-indole alkaloids, topsentin-A (1), -B 1 (2), and -B2 (3) have been isolated from the Mediterranean sponge Topsentia genitrix and their structure determined by spectroscopic methods. These compounds are weakly toxic for fish and for dissociated cells of the freshwater sponge Ephydatiafluviatilis and thus might be partially responsible for the chemical defense of the sponge.