Fructose 1,6-bisphosphatase mRNA and enzyme activity in HL-60 cells were rapidly and markedly induced by calcitriol (formerly known as la,25-dihydroxyvitamin D3). The activity reached 70-80 times the basal level after 96 h. The enzyme activity in the cells incubated for 96 h with calcitriol decreased immediately after its withdrawal but after a 24-h incubation the activity in the cells continued to increase slightly and then decreased slowly. Calcitriol increased the enzyme activity dose-dependently with maximal stimulation at 10 nM and half-maximal at 2.1 nM. The rate of synthesis of fructose 1,6-bisphosphatase almost paralleled the increase in inRNA level during treatment with calcitriol. When calcitriol was removed from media after incubation for either 24 h or 96 h, fructose-1;6-bisphosphatase mRNA and fructose-l,6-bisphosphatase synthesis decreased rapidly to the basal level. The enzyme was only slightly degraded in the cells incubated with calcitriol for 24 h followed by the subsequent culture without calcitriol but it was degraded with a half-life estimated to be approximately 64 h in the same cells followed by culturing with calcitriol. In the cells incubated for 96 h, the same degradation rate (i.e. half-life =64 h) was observed irrespective of the following culture with or without calcitriol. Calcitriol did not affect the degradation rate of total soluble proteins.Fructose 1,6-bisphosphatase (FBPase) is one of the ratelimiting enzymes in hepatic gluconeogenesis. The in vivo level of FBPase is under nutritional and hormonal controls. The intracellular concentration of the enzyme in the liver increases under gluconeogenic conditions including fasting, a high-protein diet and alloxan diabetes [l]. The enzyme concentration is also increased by the injection of glucagon, glucocorticoids and thyroxine [2]. El-Maghrabi et al. showed that FBPase mRNA was increased in livers from adult diabetic rats and was reduced to control levels after insulin treatment [3]. Recently, they observed the accumulation of FBPase mRNA in primary hepatocyte cultures incubated with cAMP and showed the presence of CAMP-responsive elements in the 5'-flanking region of the rat FBPase gene [4].FBPase is present in fetal liver and increases exponentially during fetal development [ 5 ] . In organ culture from fetal mouse liver, the activity of FBPase is remarkably elevated in the presence of dibutyryl cAMP [6, 71. FBPase activity, however, increases during the culture even in the absence of an inducer, although at lower rates [6]. The increase in intracellular FBPase concentration, especially in fetal development, might also be regulated by another factor (s) in addition to elevation of CAMP.