The relationship between immunogenicity of Shigella paradysenteriae, the branched synthetic polypeptide poly-L (Tyr, Glu)-polylpro-polyllys [(T, G)-Pro--L] and human albumin (HSA) interacting with macrophages and kinetics of antigen degradation and degree of binding to the cell surface was studied. Following thioglycollate inoculation into C57BL/6 mice, the peritoneal-stimllated macrophages had higher levels of hydrolases as compared to unstimulated cells. The lysates of the stimulated macrophages catabolized the three labeled antigens faster than did the lysates of unstimulatec cells. However, when degradation of labeled antigens by macrophage cells was assessed, no direct correlation could be demonstrated between the level of cell hydrolases and rate of (T, G)-Pro--L or HSA catabolism. The immunogenicity of antigens following their uptake by unstimulated and stimulated macrophages was determined by transfer of the antigen-bearing cells into irradiated and nonirradiated syngeneic recipients. No correlation was apparent between the rate of antigen degradation and the capacity to evoke a humoral response. Similarly, no correlation could be demonstrated between the amount of antigen bound to the macrophage cell surface and the immunogenicity of the antigen. It is suggested that neither the rate of antigen catabolism by macrophages nor the amount of antigen bound to the macrophage membrane is the sole factor which determines the immunogenicity of antigens interacting with macrophages.