The effect of covalent binding of sialoglycopeptide (GP) derived from fetuin to the liposome surface on the clearance of liposomes from the circulation of rats was investigated. Small unilamellar vesicles (SUV) and two types of multilamellar liposomes (MLV, LMLV) were prepared and coupled with GP without changing the size distribution of the liposomes. The leakage of carboxyfluorescein (CF) from these GP-modified liposomes in plasma was measured in vitro. The clearance of intravenously injected GP-modified liposomes was followed by monitoring entrapped CF and incorporatd [3H]cholesteryl oleate ([3H]CHOL) in the liposomes.It was shown that CF release from GP-modified SUV increased slightly with increasing amount of GP-modification. On the other hand, CF was released more rapidly from GP-modified MLV and LMLV. The circulation times of MLV and LMLV were reduced by the surface modification of the liposomes with GP. In contrast, the clearance of SUV was inhibited significantly by incorporation of GP on the surface of the liposomes. The clearance pattern of negatively charged liposomes containing dicetyl phosphate, which had equivalent ζ potential and similar size distribution to GP-modified SUV, suggests that the prolonged circulation time of GP-modified SUV is not attributable to the negative surface charge of liposomes. These results suggest that surface modification of SUV with sialoglycopeptide derived from fetuin may be a useful technique for designing liposomes with a long circulation time.