The effect of a range of E. coli L-asparaginase (EC2) concentrations on mouse splenocyte blastogenesis was examined at various concentrations of both T- and B-lymphocyte mitogens. At optimal mitogen concentration and with 0.1 unit EC2/ml inhibition of the Con A (T cell) response was 2.5 times as great as inhibition of the LPS (B cell) response. Another T-cell stimulant, periodate, was inhibited in a manner comparable to Con A while the PHA response was inhibited to an intermediate degree. In vivo the PFC response was suppressed to 19% of normal when 100 units EC2 was given with SRBC. However, when T-cell participation in this response was by-passed by simultaneously giving LPS, the residual activity rose from 19% to 52%, again suggesting that T-lymphocytes were the more severely depressed population. These observations demonstrate that a nonspecific stimulant of the immune system may alleviate the depression of immune responsiveness induced by a chemotherapeutic agent.