Two distinct cell signals have been isolated from the sponge host of the tropical sponge/macroalga symbiotic association Haliclona cyiniformis/Ceratodictyon spongiosum. These water soluble cell signals (M, between 500 and 1000) modify separate steps in the carbon metabolism in both C spongiosum and the microalga, Symbiodinium from the coral Plesiastrea versipora. The first signal, host release factor (HRF), stimulates the release of compounds derived from algal photosynthesis; the second signal, photosynthesis inhibiting factor (PIF), partially inhibits photosynthesis. Both HRF from the sponge H. cymiformis and HRF from the coral P. versipora stimulated the release of glycerol from Symbiodinium suggesting that they act at a similar step in the metabolism of this alga. This is the first time that such cell signals have been isolated from a sponge. We suggest that they belong to a family of similar cell signals from symbiotic invertebrates that modify algal carbon metabolism. (c) 2006 Elsevier Inc. All rights reserved.