Liposomes consisting of 14C-labeled egg yolk phosphatidylcholine were incubated with whole human plasma or plasma subfractions. The transfer of liposomal phospholipid to plasma high density lipoprotein was determined by gel filtration. Whole plasma degraded the liposomes considerably faster than isolated high density lipoprotein. The phospholipid-transferring activity of whole plasma could be recovered in an equivalent mixture of isolated high density lipoprotein and lipoprotein-free plasma. The transfer stimulating activity in lipoprotein-free plasma was not associated with albumin but with a component of higher molecular weight. Upon incubation of lipoprotein-free plasma with liposomes this component appeared to be adsorbed to the liposomes and could thus be separated from the bulk protein by gel filtration. This binding to liposomes is taken as an indication that the component acts by modifying the lipid-water interface thus facilitating the insertion of the lipoprotein into the liposomal bilayer.