AbstractIn response to concanavalin A (Con A) mouse spleen cells produce increased amounts of urea. This increase results from arginase activity degrading arginine into urea and ornithine. It is mediated by a soluble protein factor, characterized by its heat stability (10 min at 80°C) and a molecular weight of approximately 32000. The factor is produced by T cells and acts on a cell population mainly present in bone marrow and spleen. Splenocytes collected from skin allograft recipients during rejection produce more urea in response to Con A than those obtained from normal or syngeneically grafted mice. The maximum urea increase is observed just before and maintained during rejection, declining rapidly thereafter. This phenomenon is explained (a) by a 10–15‐fold increase in arginase‐enhancing factor production by Con A‐stimulated allograft recipient spleen cells and (b) by an increased responsiveness of these splenocytes to the ly