Molecular data from shell matrix proteins provide new possibilities for delineating biomolecular changes in information-rich fossils. Protein separations for ancient and modern Polinices duplicatus and Mercenaria campechiensis suggest degradation of the hydrophilic fractioo and an increase in the charge of the hydrophobic fraction with time. A comparison of aspartic acid concentrations between the fossil and modern shells indicates a decrease (17.8 nmol/mg) in the hydrophilic fraction and an increase (0.5 nmol/mg) in the hydrophobic fraction. Consideration of this trend and the observation that δ13C values of amino acids from the hydrophobic fraction of the modern shell are higher than those of the fossil may indicate that some of the 13C-depleted material from the hydrophilic fraction was reincorporated into the hydrophobic fraction during diagenesis. Loss of isotopically depleted products from the modern hydrophobic fraction is also likely to have taken place. Large differences (8‰ or more) in δ13C values of corresponding amino acids between hydrophobic and hydrophilic fractions of the modern shell likely reflect variations in the extent of fractionation within unique pathways of synthesis. The ability to address long-standing questions regarding the history and origins of ancient organic material from fossils will require new or unique combinations of approaches such as those presented here.