In this paper the regulation of the activity of bovine brain 63kD PDE isozyme by phosphorylation and dephosphorylation was studied. The experimental results are as follows: 1. The 63kD PDE isozyme was phosphorylated by the purified bovine brain Ca²⁺/CaM-PK Ⅱ in the presence of Ca²⁺ and CaM, the maximal phosphate incorporation was 1mol/mol subunit of the 63kD PDE isozyme. 2. The phosphorylated 63kD PDE isozyme was dephosphorylated by calcineurin in the presence of Ni²⁺ and CaM. 3. The AC₅₀ for Ca²⁺ of the phosphorylated form of the 63kD PDE isozyme was higher than that of the nonphosphorylated form of the 63kD PDE isozyme.