We show that the Hofmeister series of ions can be used to explain the cellular changes in exocytosis observed by single-cell amperometry for different counteranions. The formation, expansion, and closing of the membrane fusion pore during exocytosis was found to be strongly dependent on the counteranion species in solution. With stimulation of chaotropic anions (e.g., ClO4-), the expansion and closing time of the fusion pore are longer, suggesting chaotropes can extend the duration of exocytosis compared with kosmotropic anions (e.g., Cl-). At a concentration of 30 mM, the two parameters (e.g., t(1/2) and t(fall)) that define the duration of exocytosis vary with the Hofmeister series (Cl- < Br- < NO3- <= ClO4- < SCN-). More interestingly, fewer (e.g., N-foot/N-events) and smaller (e.g., I-foot) prespike events are observed when chaotropes are counterions in the stimulation solution, and the values can be sorted by the reverse Hofmeister series (Cl- >= Br- > NO3- > ClO4- > SCN-). Based on ion specificity, an adsorptionrepulsion mechanism, we suggest that the exocytotic Hofmeister series effect originates from a looser swelling lipid bilayer structure due to the adsorption and electrostatic repulsion of chaotropes on the hydrophobic portion of the membrane. Our results provide a chemical link between the Hofmeister series and the cellular process of neurotransmitter release via exocytosis and provide a better physical framework to understand this important phenomenon.