Safety concerns for immunoglobulin preparations have led us to study partition/inactivation of two prototype retroviruses, mouse xenotropic type C and lymphadenopathy-associated virus (LAV) of the acquired immunodeficiency syndrome (AIDS), during manufacture and storage of immunoglobulins. Reduction of infectious retrovirus titers were 10(5) to 10(8)-fold through Cohn-Oncley cold ethanol fractionation from plasma to fraction II, 10(3) to 10(5)-fold through incubation at pH 4.0 and another 10(4)-fold through incubation of the purified liquid immunoglobulin preparations at 27 degrees C or 45 degrees C. The results support the clinical and epidemiological evidence that therapeutic immunoglobulin preparations do not transmit AIDS virus.