The influence of certain physicochemicol and biologic properties of protein antigens on their handling by the glomerular mesangium was studied in rats. The following ferritin-based probes were employed: (a) naturally occurring ferritin isomers to examine the role of melocular size; (b) chemically cationized ferritins (pI 7.1 and 8.8) to test charge effects; (c) glutaraldehyde (GA-)coupled ferritin as an analogue of a toxic molecule. Molecular size was found to be a major determinant of the extent and rapidity of antigen uptake, but had only a minor influence on persistence. The rapidity of uptake and antigen persistence was charge dependent, but to a limited extent. Biologic activity of macromolecules appears to be a very important determinant of mesangial handling since GA-treated ferritin was taken up much more rapidly and to a greater extent than native ferritin, and could persist for very prolonged periods.