We have demonstrated that biotinylated asparaginase binds to mouse monocytes. Also, asparaginase bound to peritoneal exudate, resident, splenic, bone marrow and pulmonary macrophages, but not to neutrophils or lymphocytes. Labelled asparaginase binding to peritoneal exudate macrophages was inhibited by 20-fold excess of unlabelled asparaginase. The binding of asparaginase to monocytes from mice injected with lactic dehydrogenase virus (LDV) or carrageenan was decreased. This decreased binding following treatment with LDV or carrageenan was reversed when mice were treated with diethylstilboestrol. In-vivo asparaginase clearance in mice infected with LDV was impaired as compared with that in uninfected mice. Neither strain nor age differences affected the binding to monocytes. The results suggest that the ability of asparaginase to bind to monocytes in vitro may reflect clearance function in vivo.