Herpes simplex virus infections can be treated with a number of drugs, but as for all pathogens, there is a constant need for new therapies. In the search for lead compounds some peptides have proven to possess an antiviral effect, but it is still unclear what mechanisms are responsible for this effect. We wish to report on the use of principal properties of amino acids for developing quantitative structure-activity relationships (QSAR:s) as a tool for modelling peptide activity and predicting the activity of new peptides. In order to test the reliability of the method, new peptides have been designed by using multivariate methodology, synthesized and tested for a number of responses. Two of the new peptides synthesized were active at lower concentrations than experienced before regarding entry and herpes simplex virus activity, but they were not able to completely inhibit viral infection. This may reflect differences in mode of action of peptides depending on the amino acid content.