The Sp185/333 system of genes, messages and proteins are expressed in the coelomocytes of the purple sea urchin, Strongylocentrotus purpuratus, and is an extraordinary example of diversification of a putative innate immune response system in an invertebrate. Reviewed here, is the current understanding of this complex system as illustrated by sequence comparisons of the genes, messages and deduced proteins with descriptions of diversity, including preliminary results on genomic organization and descriptions of 185/333 in other echinoids. Sp185/333 gene expression in adults and embryos occurs in response to immune challenge and includes changes in the frequencies of Sp185/333-positive coelomocytes in the adults. The diversity of the Sp185/333 protein repertoire in coelomocytes is far greater than the sequence diversity encoded in the genes, which may be the result of rapid gene recombination, RNA editing and/or low-fidelity transcription, plus post-translational modifications. This review concludes with preliminary results and speculations on protein function.