Sweat secretion helps maintain the skin surface ecosystem and provides thermoregulation in humans and the Equidae. Mediators of sweat secretion act by activating receptors coupled to phospholipase-C, which results in the breakdown of phosphatidylinositol 4,5-bisphoshate to create inositol 1,4,5-trisphosphate (IP3) which stimulates a Ca2+ signaling process that is biphasic {Putney, 1981; Berridge, 1984}. This biphasic response involves the release of Ca2+ ions from an intracellular organelle, the endoplasmic reticulum (ER), followed by the entry of calcium ions across the plasma membrane. Much is known about the first phase of intracellular calcium release from an intracellular organelle, an effect mediated by IP3 acting on the IP3 receptor {Berridge, 1987}. The resultant rise in calcium is maintained by calcium influx and it is this sustained elevation of calcium which activates the secretory mechanism. The mechanisms regulating the Ca2+ entry process in sweat glands are not well understood. It is commonly accepted that the degree of emptying of the intracellular Ca2+-stores, generated by IP3 pathway, initiates a signaling process that regulates the rate of Ca2+ entry across the plasma membrane. This process is known as capacitative Ca2+ entry or store-operated Ca2+ entry (SOCE) {Putney, 2005; Parekh, 2005}. Despite the signaling processes underpinning SOCE having been researched over the last two decades, it is only fairly recently that the key molecular components been identified. We investigated the role of SOCE in horse sweat gland cells from control animals and those that had developed anhidrosis, an inability to produce sweat. The cells used in this study were previously grown from horses destroyed for humane reasons (Wilson et al., 1993) and the methods used to initiate cultures of equine sweat glands are based on protocols elsewhere for human glands (Lee et al., 1986). Western blotting and PCR techniques confirmed the presence of STIM 1 and 2, Orai 1, 2 and 3 and TRPC1 proteins in cell lines derived from control and anhidrotic animals. However, the results indicated a reduction in STIM1 mRNA and protein expression, as well as a decrease in the localisation of STIM1 in the ER of anhidrotic cells compared to control cells. The functionality of the SOCE pathway in both cell lines, in response to agonist stimulation was investigated using FURA-2AM calcium-imaging techniques. Increases in [Ca2+]i could be abolished in the presence pharmacological blockers of SOCE and that anhidrotic cells showed a significant decrease in the [Ca2+]i FURA-2 ratio in response to agonists when compared to control cells. The results suggest that a reduction of STIM1 expression in the SOCE pathway may play a role in anhidrosis in horses.