When treated with IL-3 plus GM-CSF, K562 myeloblast cells acquired the ability to mobilize nonmitochondrial stores of intracellular Ca2+ in response to added Ins(1,4,5) P3. Untreated K562 cells are capable of sequestering intracellular Ca2+ but released none of this Ca2+ in response to Ins (1,4,5)P3. Untreated K562 cells were shown to have no detectable specific [3H]Ins (1,4,5)P3 binding sites and no InsP3 receptor mRNA as assayed by Northern blot and PCR. However, following IL-3 and GM-CSF treatment, both a single class of low nM KD Ins(1,4,5)P3 binding site and a 10 kb InsP3 receptor mRNA were detectable. The results suggest that IL-3 and GM-CSF regulate the expression of the Ins(1,4,5)P3 receptor gene. © 1992 Academic Press, Inc.