Elevated levels of intracellular Ca(II) are a prominent feature of apoptosis, a natural form of cell death involved in many physiological and pathological processes. Serine proteases play crucial roles in apoptosis and have been implicated in the genomic DNA degradation and the massive protein degradation that occur during apoptosis. In this study, the eects of the elevated level of Ca(II) on the activity and inhibition of serine proteases were examined by spectrophotometric methods. The eects of the elevated levels of Ca(II), Mg(II), K(I), and Na(I) on the activity and inactivation of three representative members of serine proteases were determined. The level of serine protease activity in CEM-C7-14 leukemic cells was also evaluated in the presence and absence of dexamethasone-induced apoptosis, and also in the presence of A23187, a Ca(II)-ionophore. Among the four metal-ions studied, only Ca(II) was found to signiยฎcantly enhance the activity of mammalian serine proteases. Ca(II) was also found to signiยฎcantly protect the enzymes from inhibition, while the other three metal-ions showed no signiยฎcant eect on the inactivation of the enzymes. Compared to the control sample, the enzymic activity was found to be higher during apoptosis, and in the presence of the Ca(II)-ionophore. Results of this study indicate that Ca(II) can signiยฎcantly enhance the catalytic eciency of serine proteases during apoptosis.