Immunological assays are highly favoured for their ability to readily discriminate subtle structural differences in complex biopolymers, such as proteins and polysaccharides. Immunological reactions previously reported with extracts from biominerals at least 70 Myr old have fuelled hopes that such biopolymeric structures can survive the process of fossilization. We have raised antibodies against biopolymers from a range of Recent brachiopod shells to reconstruct a fine-grained pattern of phylogenetic relationships. Using the same antibodies, the phylogenetic affinities of fossil relatives were tested. Immunological reaction patterns for Plio-Pleistocene shells were essentially identical to the patterns of modern shells (although the breadth of reactivity was narrowed) and entirely consistent with current systematic interpretations. Older samples (>4-21 Myr) were immunologically reactive, but failed to satisfy the criterion of systematic specificity. Our results provide an unequivocal demonstration that original macromolecular structures capable of yielding systematic information are preserved and accessible for immunological analysis for at least two million years. Non-specific reactions observed with the older material may relate in part to formation of mineral-induced diagenetic determinants (MIDDs).