Previous studies have shown that certain lipids and fatty alcohols have microbicidal activities against a number of pathogens. In this study, virucidal activities of fatty alcohols and lipids were tested against HSV types 1 and 2 at various concentrations, times, and pH levels. The aim was first, to determine which compounds are most virucidal against HSV and could possibly be used as active ingredients in topical drug formulations and second, to attempt to throw light on the mode of action of virucidal lipids. Good agreement was found between the activities for HSV-1 and HSV-2. The activity of a compound depends on the concentration and time of contact and most of the compounds are more active at pH 4.2 than at pH 7. This information may be helpful in the formulation of pharmaceutical dosage forms for treatment of herpes lesions in skin and mucosa. The difference between the polar groups of alcohols and fatty acids, i.e. hydroxyl group versus carboxyl group, and the corresponding difference in their hydrophile-lipophile balance (HLB) may explain their different virucidal activities against HSV. However, in most cases HLB numbers cannot explain the different virucidal activities of fatty alcohols and lipids, particularly not their increased activity at low pH. It is more likely that the acidic environment makes HSV more sensitive, possibly by ionic changes in the envelope proteins.