Surfactant preparations, which are effective in the treatment of respiratory distress syndrome (RDS), contain phospholipids and small amounts of the 2 hydrophobic surfactant proteins SP-B and SP-C. At present, surfactant preparations are obtained from animal lungs. However, since information concerning the structure of SP-B and SP-C is now available, it appears possible to design analogues that can replace the native proteins and so formulate a synthetic peptide/lipid surfactant. This would circumvent problems associated with current purification procedures and also facilitate the production of quantities sufficient for evaluation of surfactant therapy in other respiratory diseases. SP-C analogues which effectively accelerate the spreading of surfactant lipids and exhibit physiological activity in animal models of RDS have been developed. However, the in vivo activity of surfactant preparations based on SP-C analogues are inferior to those of surfactant preparations derived from natural sources. This may be caused by lack of covalently linked palmitoyl groups in the SP-C analogues tested and/or that SP-B is required for full activity. The larger size of SP-B compared to SP-C makes the design of SP-B analogues more demanding. Surfactant preparations containing single peptides that may resemble SP-B have shown promising results in vitro and in vivo. Identification of further SP-B analogues as well as suitable combinations of SP-B and SP-C analogues appear to be important topics for future studies.