In the present study, we have investigated the role of complement (C) and possible C receptors present on rat liver endothelial cells (EC) in the clearance and tissue distribution of soluble aggregates of IgG (AIgG). To study the effect of elimination of AIgG by EC in vivo, Kupffer cell (KC)-depleted rats were used, with or without an intact C system (These rats will be referred to throughout this report as EC-rats.) In EC-rats with an intact C system, clearance of AIgG (2000-3000 kDa, 20-27 IgG molecules/aggregate) occurred in a biphasic manner with a first T½(T1)of 9.4 ± 2.3 min and a second T½(T2) of 44.7 ± 16.0 min. In EC-rats without an intact C system [cobra venom factor (COVF)-treated group], clearance of AIgG was significantly delayed with a T1 of 25.3 ± 9.9 min (p 0.005) and aT2 of 124.5 ± 18.4 min (p 0.001). There were less degradation products of AIgG in the circulation in EC-rats treated with COVF as compared to EC-rats with an intact C system. Eight minutes after injection, 27.5 ± 11.6% of the injected AIgG was found in the livers of EC-rats while 15.1 ± 3.2% was found in the livers of the COVF-treated group. Double immunofluorescence studies indicated that AIgG in the liver was associated with EC in the rats with an intact C system. Clear deposits of C3 and lesser amounts of Clq accompanied the deposition of AIgG. In COVF-treated EC-rats, AIgG together with Clq was also associated with EC but no detectable C3 was seen. These data suggest clearance of AIgG via Fc and C receptors present on EC in vivo.