A new economical and reproducible micromethod for the preparation of human macrophage cultures in wells of a microtiter plate is described. The technique has been employed for the study of events which occur in the interaction of lymphocytes with macrophages in PHA-stimulated immune interferon production and blastogenesis. By comparison with the current Leighton tube macroculture systems, the microculture technique yielded a 7-fold increase in the number of macrophage cultures and a 5-fold increase in the number of T lymphocyte macrophage cultures from a given volume of blood. The replicability from sample to sample with regard to 3H-thymidine incorporation and amount of interferon produced is better in the microculture system than in the Leighton tube system. Such a microculture technique will thus provide a system whereby ready analysis of monocyte-macrophage function and interaction with lymphocytes in numerous disease states can now be realized.