Previous studies suggested that cell adhesion in the marine sponge, Ophlitaspongia tenuis, is mediated by a 35 kDa cell surface protein which interacts with an extracellular sulfated polysaccharide. This paper describes a simple and efficient procedure for isolating both putative cell adhesion molecules from detergent lysates of O. tenuis cells, the procedure being based on the fortuitous affinity of the sponge polysaccharide for heparin. The purified polysaccharide inhibits O. tenuis sponge cell aggregation, is highly sulfated and represents a glycosaminoglycan containing glucuronic acid. N-sulfated glucosamine and, possibly, glucose. The purified 35 kDa protein has a high affinity for the sponge polysaccharide and also, selectively interacts with dextran sulfate, a polysaccharide that has been shown previously to both bind to the sponge cell surface and inhibit aggregation of O. tenuis cells. Collectively, the data supports the hypothesis that the 35 kDa molecule is the major cell adhesion protein in O. tenuis. Preliminary data also suggests that the sponge contains an endogenous glycan hydrolase which can cleave the sponge polysaccharide.