A method has been defined for infecting primary mouse peritoneal macrophages with amastigotes of Leishmania donovani in vitro, and analysing the response of the infected macrophages to treatment with drugs. The growth of intracellular amastigotes was inhibited by all clinically used antileishmanial drugs. Toxic effects on macrophages were observed with some drugs. Other experimental antileishmanial compounds were active in this system. This test is proposed as an initial screening test for the discovery of novel antileishmanial compounds.