In the real cellular conditions, the biological macromolecules, as DNA and proteins, live in high concentrations of biomolecules, salts and so on. In particular organisms and cellular systems, which have adapted to extreme environmental conditions, accumulate particular organic solutes, known as osmolytes, at moderate to high concentrations to raise the osmotic pressure in the cytoplasm. This molecular crowding affects stability and activity of biological macromolecules. The goal of this work is to study the simultaneous effect of a natural osmolyte and polyamine on the stability of DNA. Particularly, we report a calorimetric study of the dependence of the thermal stability of a calf-thymus DNA (ct-DNA) on changing the osmolyte concentration in the presence of a constant concentration of a 1,5-diaminopentane, commonly known as cadaverine, which belongs to the class of natural polyamines. The osmolytes utilised were betaine, D-arabitol, L-arabitol and D-sorbitol. The effect on the DNA thermal stability of cadaverine and of each osmolyte separately was also reported for comparison. Our data show that cadaverine does not lose its own ability to protect DNA by the destabilising action of high concentration of osmolyte molecules synthesised in conditions of environmental stress. (C) 2004 Elsevier B.V. All rights reserved.