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The ability of nedocromil sodium, a new anti-inflammatory agent for the treatment of asthma, to inhibit activation of human eosinophils and neutrophils in vitro, has been studied using an adherence reaction (the "rosette" technique) as well as a cytotoxicity assay. We have also investigated the capacity of nedocromil sodium to inhibit IgE-dependent histamine release from human lung mast cells. The drug was a potent inhibitor (IC50 approx 5 × 10-9M) of fMLP-induced enhancement of eosinophil and neutrophil complement (C3b) and IgG (Fc) rosettes. There was also a comparable inhibition of enhancement, by fMLP, of eosinophil and neutrophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Although nedocromil sodium also inhibited histamine release from human lung mast cells in a dose-dependent fashion its activity was relatively weak (IC30 5 × 10-6M) compared to its effect on granulocytes. These experiments support the view that the principal mode of action of nedocromil sodium is its capacity to inhibit the activation of inflammatory cells. [ABSTRACT FROM AUTHOR]