A free radical reaction generated by a mixture of Cu2+, hydrogen peroxide, and ascorbate causes an abrupt reduction in the anti Xa activity of heparin by about one-half, and in molecular weight by about one-third. The product, which has the characteristics of a "low molecular weight" heparin, differs little in constitution from the intact heparin, on the basis of NMR evidence that includes data for fractions of the polymers. The free radical attack appears to occur adjacent to, rather than directly upon, some residues of alpha-L-iduronic acid 2-sulfate. Substitution of the Cu2+ with Fe2+, results in a less selective alteration of the heparin. Dermatan sulfate undergoes more extensive degradation than heparin with the Cu-reagent, although its anti Xa a potency is less drastically reduced. Overall, the results are more consistent with a high degree of regioselectivity in the interaction between heparin and Cu2+ ion, than with a delocalized counter-ion interaction.