Motivated by our earlier demonstration that calmodulin (CaM) antagonist-trifluoperazine (TFP) effectively inhibits cell proli feration and DNA synthesis in human stomach carcinoma MGC-803 cells with simultaneous induction of normalized cell morphology, this work was designed to investigate the mechanisms of TFP effect on MGC-803 cells By using biochemical assays, CaM and phosphodiesterase(PDE) activities in TFP treated MGC-803 cells were quantitatively analyzed with comparison to untreated control cells. TFP treated mouse ascitic hepatoma cells were analyzed as parallel. Results indicate that TFP selectively inhibits Ca²⁺/CaM-dependent PDE activity rather than the PDE-binding activity of CaM in drug-treated cells of both types. However, both MGC-803 and mouse hepatoma cells exposed: to aminophylline (2mmol/L) for 3 days or shorter time showed decrease in PDE-binding activity of CaM. The possible mechanisms concerning TFP effects and their role in regulating cell proliferation of MGC-803 cells were discussed.