IgE-dependent histamine-releasing factor(HRF) was initially described as a secretagogue for secretion of histamine from IgE+ basophils from a subset of allergic donors. Previously, we identified that S98 residue of HRF was phosphorylated using anti-HRFpS98 antibody which specifically recognizes the phosphorylated serine residue of HRF and HRFS98A mutant construct. In vitro kinase assay, only wild type HRF was phosphorylated by PKC, and S98A HRF was not affected by PKC. In this study, we attempted to characterize the phosphatase which specifically dephosphorylates HRF by immunoprecipitation and pull-down assay. In RBL-2H3 cells, HRF interacted only with calcineurin (also called as PP2B, calcium/calmodulin-dependent phosphatase) but not with PP1 or PP2A. The results suggest that HRF is most likely dephosphorylated by calcineurin.