Proteinase-activated receptor (PAR) type 2 (PAR-2)(ref 1), which is activated by the action of trypsin and activating peptides (AP), has been shown to mediate ion secretion in a variety of secretory epithelial cells in the GI tract and airways (2). However, their action on human sweat gland secretory cells is unknown. This study, investigated the effects of PAR-2 stimulation on ionic secretion in a human sweat gland cell line NCL-SG3 (NCL) (3) determined by Ussing chamber experiments. NCL cells were grown to confluence on permeable supports, mounted in Ussing chambers, bathed with 95%O₂/5%CO₂-bubbled Krebs-Henseleit solution at 37^oC and allowed to equilibrate under open circuit conditions. Transepithelial potential difference was clamped to 0mV using a voltage current amplifier. The current to maintain this potential (short-circuit current, Isc) was recorded. Resistance was calculated by measuring the current in response to a 0.2mV excursion from the holding potential. Positive deflections in Isc were defined as anions moving from the basolateral to the apical side. Results are expressed as means±sem and statistical analysis performed using Student’s t-test. P values <0.05 indicate significance. Cells were stimulated by adding compounds to the basolateral baths. NCL cells exhibited low basal resistances of 65.8±7.5Ω cm^-2, basal Isc levels of 9.3±2.4μA cm^-2, which was unaffected by the presence of the sodium channel blocker amiloride (10μM), demonstrating that NCL cells do not have a basal Na⁺ conductance (n=14). Trypsin (100μM) and AP (100μM; Bachem, Germany) added to the basolateral aspect of the cells caused increases in Isc of 2.54±0.45μA cm^-2, 2.43±0.39μA cm^-2 (n=7; P<0.05, respectively). An inactive PAR-2 peptide (100μM) failed to elicit any response when added to the basolateral side. Both trypsin and the AP failed to elicit any change in Isc in chloride-depleted solutions. The results of this study demonstrate that PAR-2 receptors are present in this sweat gland cell line and that stimulation of these receptors at the basolateral membrane in these cells can produce chloride secretion.