Conformational properties and the energy barriers between the anti and the syn configurations of 3TC, ddC, AZT and d4T have been examined using the density functional theory. For 3TC, ddC and AZT the global minimum structure is the syn configuration of pyrimidine unit. Only thymine ring of d4T is at the anti conformation. Changing from the syn to the anti configuration, the furanose ring conformation is not generally affected for all compounds under consideration. (C) 2004 Elsevier B.V. All rights reserved.