A comparative immunochemical study was conducted with an antiserum prepared for the first time against growth hormone (GH) from a phylogenetically ancient fish, the blue shark (Prionace glauca). The result of immunodiffusion studies revealed extensive immunochemical relatedness of GHs from species representing each of the major vertebrate classes. The findings obtained with a homologous radioimmunoassay (RIA) system did not show good correlation with those obtained by immunodiffusion. However, a heterologous system employing the same antiserum and a purified rat GH for standards and for the tracer, gave results that were in good agreement with the findings based on immunodiffusion. Interestingly, in the heterologous RIA, the purified GH of a modern bony fish (Tilapia) as well as the presumptive GH in pituitary extracts of several other modern bony fishes (teleosts), showed significant relatedness to shark GH only when employed at very high concentrations. The rat tibial plate-stimulating activity shown by a shark pituitary extract was completely blocked with injections of antisera to purified shark or turtle GH. Furthermore, purified shark GH showed a very significant stimulation in the rat tibia assay, in contrast to the lack of stimulation reported earlier by several investigators using pituitary extracts of teleostean species and the relatively low degree of stimulation shown recently with a highly purified GH from a teleost (Tilapia). The data obtained thus far based on immunochemical and biological studies suggest that there must be some significant differences in the structure of shark GH compared to the structure of GH from modern bony fishes, in spite of the existence of substantial similarities. © 1978.