Glucuronoxylomannan (GXM) is the most prominent of the capsular constituents and is the primary target for anticapsular antibody and the most likely mediator of capsule-complement interactions. The goal of this chapter is to describe (i) variability in the interactions of GXM antibodies with the capsular matrix, (ii) the mechanisms for interaction of the capsule with proteins of the complement system, (iii) the nexus of the anticapsular antibody and complement system in capsule interactions, and (iv) the consequences of antibody and complement binding for modification of the capsular matrix. Differential interference contrast (DIC) systems detect optical gradients, preserve its sign, and convert the gradients into visible intensity gradients. Binding of antibody to the capsule edge to produce the annular rim could be due to localization of epitopes only at the capsule perimeter; monoclonal antibodies (MAbs) producing puffy patterns may bind to epitopes located throughout the capsule. Evidence of the importance of the complement system is provided in several reports of the course of cryptococcosis in normal versus complement deficient mice. Activation of the alternative pathway leads to conversion of C3 to C3b, which in turn, binds to the cryptococcal cell. Incubation of acapsular cryptococci in adsorbed serum leads to deposition of C3 onto the cell wall, but C3 binding occurs via the slow kinetics characteristic of the alternative pathway. In contrast, encapsulated cryptococci are unable to adsorb the antibodies from normal serum that mediate the rapid, early deposition of C3 onto acapsular cryptococci.