The phylogenetic relationships of living, calcareous‐shelled brachiopods have been assessed on the basis of immunological responses from intracrystalline macromolecules. Calculations of immunological distances between representatives of the order Terebratulida have revealed a primary threefold division which correlates precisely with a proposed subdivision of the order into three superfamilies but refutes attempts to establish a fourth superfamily. This conclusion was confirmed by carrying out immunological investigations of small shell fragments from other brachiopod genera which were so rare that no antisera could be prepared. The immunological results also indicate a fundamental subdivision of the long‐looped brachiopods, with one group perhaps being derived from short‐looped terebratuloids rather than long‐looped terebratelloids. Sero‐taxonomy of skeletal macromolecules provides an ideal method of acquiring molecular phylogenetic data in many groups because a large number of taxa can be surveyed in a short period of time, and microscopic pieces of shell contain sufficient antigenic determinants for many reactions. The technique can also be applied to specimens which have been stored without special treatment in museum collections, making the technique particularly applicable to rare taxa for which no other form of molecular data is available. □Immunology, Brachiopoda, taxonomy, intracrystalline molecules.