Abstract.Virus sterilization of blood plasma derivatives by addition of several naturally occurring fatty acids was evaluated using vesicular stomatitis virus and Sindbis virus as markers for lipid‐enveloped virus inactivation and human immunodeficiency virus (HIV). Inactivation of ≥104tissue culture infectious doses (TCID50) of marker viruses added to antihemophilic factor (AHF) concentrates, with 60–100% retention of AHF activity, was achieved with oleic, 11‐eicosenoic, linoleic, linolenic, palmitoleic and arachidonic acids. Elaidic, gamma‐linolenic, palmitic, and arachidic acids and another fat‐soluble compound previously reported to inactivate virus, butylated hydroxytoluene, were less effective. A long chain mono‐ but not a di‐ or triglyceride also displayed virucidal properties. Evaluation of the inactivation of HIV added to an immune globulin solution on exposure to 0.033% sodium oleate for 20 min indicated inactivation of ≥1034TCID50. The degree of virus inactivation depended on the sample composition. A favorable balance was achieved between degree of virus inactivation and retention of protein function for AHF concentrate, prothrombin complex concentrate, antithrombin III concentrate, and immune globulin solution on incubation with 0.033% (w/v) sodium oleate at 24 °C for 4–6 h. Virus inactivation in whole plasma and plasma cryoprecipitate was not complete despite use of higher concentrations of sodium oleate and/or incubation at 37 °C. Reduced virus kill in these less purified derivatives probably is a consequence of their endogenous