Rat and guinea pig liver microsomes labeled with phospholipid (32)P were incubated with rat, guinea pig, and rabbit plasma in a KCl-Tris-EDTA buffer. A net transfer of microsomal phophatidylcholine and phosphatidylethanolamine to plasma was observed. In addition, an exchange of phospholipids between microsomes and plasma took place. During 20-min incubations at 37 degrees C, the exchange of phosphatidylcholine was the most extensive. Microsomal sphingomyelin exchanged with plasma sphingomyelin only very slowly. A soluble protein factor in liver, which had previously been observed to stimulate the exchange of liver mitochondrial and microsomal phospholipids, also increased the exchange of phosphatidylcholine between liver microsomes and plasma. The pronounced differences in the relative percentages of phosphatidylethanolamine of guinea pig, rabbit, and rat plasmas did not appear to be related to differences in the relative exchange of this phospholipid compared to that of other phospholipids in these plasmas.