Iopamidol-carrying liposomes were studied as potential hepatosplenographic contrast agents. Large unilamellar vesicles (0.3-1 mu) prepared from phosphatidylcholine:Dipalmotylphosphatidic acid (PC:DPPA) 9:1 and 300 MgI/mL iopamidol solution showed favorable entrapment measured as mg entrapped iodine/mg lipids (I/L). The effect of extrusion through polycarbonate membranes on liposome characteristics and in vivo distribution was investigated. Extrusion above the transition temperature of lipids reduced the average size and size distribution and increased the I/L ratio. Distribution studies of extruded and nonextruded liposomes in rats demonstrated different behavior of the preparations; extruded liposomes showed higher spleen uptake than did unextruded, while liver uptake was comparable; lung entrapment, observed with unextruded particles, was almost eliminated with extruded liposomes. Preliminary imaging studies in rats were carried out at a dose of 250 mgI/kg; typical computed tomography (CT) scans of the liver demonstrated contrast enhancement of greater than or equal to 60 HU from 90' up to 240' after injection.