This report addresses the host mechanisms which regulate susceptibility and resistance to group A streptococcal cell wall-induced polyarthritis in the rat. We have compared cell wall tissue distribution and persistence following a single intraperitoneal injection of an aqueous suspension of the cell walls into arthritis susceptible LEW/N and resistant F344/N female rats. Selected aspects of the induced inflammatory reaction were also compared. Our results suggest that development of chronic erosive polyarthritis in this model is dependent, in variable degrees, upon 1) deposition and persistence of the cell walls in synovial tissues, and 2) a relative inability of arthritis susceptible rats to neutralize the proinflammatory properties of the cell walls.