SummaryInfections byTrypanosoma lewisiare characterized by hyporesponsiveness of the immune system during the early phase of parasitaemia. Blastogenic response of normal rat spleen cells to amphiphilic and hydrophilic components of Triton X‐114 solubilized epimastigote forms ofT. lewisiwhich characterizes the early phase of infection showed that suppression of responses to mitogens Concanavalin A (Con‐A) and lipopolysaccharide (LPS) occurred exclusively with the amphiphilic fraction that consists of integral surface membrane constituents. The Con‐A‐induced suppression by the amphiphilic constituents was ablated by addition of exogenous IL‐2 or by the removal of the adherent cell population in the cultures. This suggests that the integral surface membrane components play an important regulatory role in infections withTrypanosoma lewisi, through complex mechanisms that probably involve the B cells and suppressor macrophages; the suppressor macrophages probably produce a suppressor factor that inhibits the proliferation of T helper cells and subsequently the production of inte