This report describes the chemotactic response of human alveolar macrophages (AM luminal diameter) and milk macrophages (MM luminal diameter) to a panel of chemotactic agents: endotoxin (EAS) and zymosan (ZAS) activated serum, lymphocyte derived chemotactic factor (LDCF) and formylated synthetic peptides. The locomotion studies were compared with the responses of peripheral blood monocytes. Both AM luminal diameter and MM luminal diameter exhibited an extremely poor chemotactic response to all agents in comparison with the monocytic response. When monocytes were cultured for long periods, a defective response was likewise demonstrated. The chemotactic response was significantly higher in AM luminal diameter from smokers. The stimulated locomotion was not increased by the addition of a surfactant lipoprotein to the AM luminal diameter suspension. Moreover, monocytes incubated with fat- and cell-free human milk exhibited lower chemotactic responses than normal monocytes and practically in the same range as that obtained with MM luminal diameter.