The chemical synthesis of thymine, cytosine and adenine Peptide Nucleic Acid (PNA) monomers, incorporating a protecting group strategy compatible with solid phase DNA synthesis has been achieved. PNA oligomer synthesis using novel reagents and subsequent PNA/DNA chimeric oligomer synthesis, purification and analysis are described. Ultraviolet melting studies have indicated that PNA/DNA chimeric oligomers form stable hybrids with complementary DNA. The complexes are more stable than the native DNA.DNA duplexes and mismatches involving the PNA segment are extremely destabilising compared to the native DNA.DNA mismatch. Only minor destabilisation of the complex is observed when the mismatch involved the DNA moiety of the chimeric oligomer. The chemical synthesis of 3-deoxyguanosine and 3'-deoxycytidine DNA phosphoramidites and synthesis by solid phase methodology of the corresponding 5'-2' Oligodeoxynucleotides has been successfully achieved. The oligonucleotide was analysed by Capillary Zone Electrophoresis and characterised by electrospray mass spectrometry. U.V. melting analysis indicated that the 5'-2' oligomer hybridised to complementary RNA but not DNA. The 5'-2' DNA/RNA hybrid was found to be thermally and thermodynamically less stable than the native 5'-3' DNA/RNA and RNA/RNA hybrid which could in part explain the preference for the 5'-3' linked isomer in nature.