Chronic phosphate depletion is associated with a reduced Vmax of Ca2+ ATPase in many cells. The mechanisms underlying this phenomenon are not fully understood. One of the regulators of the Ca2+ ATPase enzyme is calmodulin, and the reduced availability of calmodulin or impaired interaction between it and Ca2+ ATPase could be responsible for the impaired activity of this enzyme in phosphate depletion. The present study examined the calmodulin content of pancreatic islets and the effect of calmodulin on the Vmax of Ca2+ ATPase in islets harvested from phosphate-depleted (PD) and pair-weighed (PW) rats. The calmodulin contents in islets from the 2 groups of animals were not different. Basal levels of Vmax of Ca2+ ATPase of islets from PD rats were significantly (p0.01) lower than in PW rats. Calmodulin produced a significant (p0.01) increase in Vmax of Ca2+ ATPase in islets of PW rats but failed to do so in islets of PD rats. The results indicate that the impaired activity of Ca2+ ATPase in islets of PD rats is not due to the reduced availability of calmodulin but an impaired response of the enzyme to calmodulin is at least partly responsible for the reduction in the Vmax of the enzyme.