The effects of L-asparaginase on the T- and B-cell responses to sheep red blood cells and to bacterial lipopolysaccharide were compared in mice. Asparaginase inhibited the response to sheep cells more than the response to lipopolysaccharide. As the former response requires T-cell help whereas the latter does not, this suggests that asparaginase damages T cells more than B cells. However, in vitro, the responses of mouse peripheral blood lymphocytes to phytohaemagglutinin and to lipopolysaccharide were equally sensitive to asparaginase. The relative in vivo resistance of the response to lipopolysaccharide is therefore unlikely to be due to an inherent insensitivity of B cells compared with T cells. It is suggested that the anatomy of lymphoid tissue provides a micro-environment for B cells that partly protects them from the effects of systemic asparagine depletion, whereas the local environment of T cells does not confer such protection.