A soluble factor, extracted from neutrophils and P388D1 cells, stimulated a transient rise in cytosolic free Ca 2 + and a small increase in the permeability to Mn 2 + in fura2-loaded neutrophils. These effects were not prevented by blockade of formylated peptide receptors by t-boc-met-leu-phe. The rise in cytosolic free Ca 2 + was partly attributed to transmembrane influx and partly due to store release. Ca 2 + store release but not transmembrane influx was inhibited by the PLC inhibitor, U73122, demonstrating a direct effect of the factor on channel opening. It was concluded that the soluble cellular factor directly stimulated Ca 2 + entry in neutrophils.