The invention provides compositions and methods for reducing RNase activity, thereby stabilizing RNA molecules in complex samples. A sample or a lysate thereof is combined and incubated with a compound capable of reacting in aqueous solution with a functional group of an amino acid residue in a polypeptide, whereby the functional group is selected from the group consisting of a primary amino group and a thiol group, whereby in the composition said compound is present at a concentration of between about 0.1 M and about 1 M.