This chapter focuses on some of the views on cation involvement in the stimulus-response of secretory cells such as human platelets and neutrophils. It should be noted that such ionophores as valinomycin, nigericin, monensin, ionomycin, or A23187 are of limited utility in investigating the role of specific cations in cellular stimulus response. The monovalent cation gradient involvement is also complicated by the highly active pump system in neutrophils which causes them to respond to, and attempt to correct for, changes in their extracellular milieu. Nonspecific esterases in the cellular cytoplasm then hydrolyze off the ester group, thus forming an in situ indicator which is pH sensitive and relatively membrane impermeable. Calibration curves must be prepared for each probe/cell pair since the compartmental distribution, and therefore the indicated pH average for the cell, depends upon the cells themselves, the nature and the concentration of the probe, the cell purification process, and the external buffer conditions.