The exchange of unesterified cholesterol molecules between rat erythrocyte ;ghosts' and human low-density lipoproteins has been studied under a number of different experimental conditions. 2. The process is pH-dependent, the rate being minimal at about pH5. 3. Cholesterol exchange does not vary greatly with temperature, the rate at 50 degrees being less than twice that at 2 degrees . 4. Large variations in the ionic strength or Ca(2+) concentration of the medium have little effect, but the exchange rate is greatly increased in the presence of a wide range of chemical compounds, e.g. urea, alcohols, acetone, dimethyl sulphoxide and tetra-alkyl-ammonium salts. 5. Acetone and dimethyl sulphoxide have a much greater effect at 37 degrees than at 8-10 degrees . 6. It is proposed that hydrophobic bonding is of great importance in maintaining the structure of ;ghosts' and lipoproteins. 7. The results are discussed in relation to current theories of membrane and lipoprotein structure.