Concentration of free cytoplasmic Ca2+ ([Ca2+]i) in Ehrlich ascites tumor cells, measured using fura-2, amounted to 170-300 nM and was increased by 50-160 nM after addition of 10 mM D-glucose or D-2-deoxyglucose but not 3-O-methylglucose at pH 7.4. In the range of external pH between 6.8 and 7.8 the increase was higher at higher pH. This increase occurred within 30-60 s after addition of hexose and lasted for at least 10 min. This [Ca2+]i rise was observed both in presence and virtual absence of Ca2+ in the external medium. Pretreatment of the cells with thapsigargin resulted in a much smaller [Ca2+]i increase after addition of glucose or deoxyglucose. The mechanism of [Ca2+] in the external medium. Pretreatment of the cells with thapsigargin resulted in a much smaller [Ca2+]i increase after addition of glucose or deoxyglucose. The mechanism of [Ca2+]i rise evoked by glucose and deoxyglucose and its importance in switching cell metabolism from oxidative to glycolytic are discussed.