We report the most comprehensive study of survival of peptide bonds and epitopes (antibody binding sites) in fossil shells from a semi-continuous New Zealand brachiopod sequence extending for 3 Ma. The study reveals for the first time long-term trends in proteins survival. The investigation focused on a sub-set of the total skeletal biomolecules, those protected from exposure to a strong oxidising agent (NaOCl); the so-called intra-crystalline component. The extent of peptide bond hydrolysis was compared with the declining immunological signal. The proportion of free amino acids increased very rapidly but between 5 and 10% of the amino acids remained peptide bound in all samples. The pattern of loss of immunological reactivity broadly mirrored the loss of peptide bonds, but overall loss of signal was much greater. Significant antibody response was observed in some but not all late Pliocene fossils (> 3 Ma), but against a panel of antisera the pattern of reactivity was lost in samples > 0.5 Ma. Alternative models of polypeptide chain scission were used in an to attempt to relate the rate of peptide bond hydrolysis to the loss of immunological determinants. The findings suggest that, despite early optimistic reports, the application of immunology to shell carbonates does not appear capable of extending into deep time.