To investigate the handling of IgA by the mononuclear phagocytic system and by hepatocytes of mice, soluble, similar sized, heat-aggregated monomeric (A-mIgA) and polymeric IgA (ApIgA) were used as akin to IgA immune complexes. The half-life of the clearance from circulation decreased from 2.5 hr to 4.2 min and from 22 min to 1.8 min after aggregation of mIgA and pIgA, respectively. Tissue localization experiments indicated that the liver was the organ predominantly involved in the uptake and catabolism of the proteins injected. The rate of the liver catabolism and/or elimination of aggregated polymeric IgA was the slowest up to 24 hr of injection. Aggregated pIgA was deposited in the kidney in larger amounts than aggregated mIgA. The participation of hepatocytes and nonparenchymal liver cells was determined after isolation and purification of these cells. The four substances injected, pIgA, A-pIgA, mIgA and A-mIgA, were predominantly localized in nonparenchymal cells when the uptake was expressed per volume of cells, due to their lower protein content. However, when the results were expressed cell to cell there was a high ratio of IgA aggregates associated with hepatocytes to nonparenchymal cells. It seems probable, therefore, that hepatocytes are almost exclusively responsible for clearance of IgA aggregates from blood.