In malacostracan crustaceans, sex differentiation is uniquely regulated by a hormone secreted by the male-specific androgenic gland (AG). An isopod AG hormone was the first to be structurally elucidated and was found to belong to the insulin superfamily of proteins. Recently, it has been found that the AGs of several decapod crustaceans express insulin-like androgenic gland factors (IAGs), whose function is believed to be similar to that of the isopod AG hormone. Here we report the isolation from the blue crab Callinectes sapidus of the full-length cDNA encoding a candidate insulin-like AG hormone, termed Cas-IAG. The predicted protein Cas-IAG was encoded as a precursor consisting of a signal peptide, the B chain, the C peptide, and the A chain in that order. While the AG was the main source of Cas-IAG expression, as found in other decapod species, the hepatopancreas of male Callinectes sapidus crabs displayed minor Cas-IAG expression. Eyestalk ablation confirmed the presence of a possible endocrine axis between the eyestalk ganglia and the AG, implying that Cas-IAG expression is negatively regulated by (a) substance(s) present in the eyestalk ganglia.