In the present study the effects of trifluoperazine (TFP) and/or cyclosporine A (CsA) on the amylase secretion of rat parotid gland lobules were investigated. Cyclosporine A, in doses of 10(-6), 3 x 10(-6) and 10(-5) M, caused a dose-dependent reduction in amylase secretion. Trifluoperazine, a well-established calmodulin antagonist, also significantly reduced amylase secretion by the gland, confirming that the secretion is calmodulin dependent. Concurrent administration of CsA and TFP showed a marked positive interaction in reducing the secretion of amylase. Thus, the hypothesis that CsA may have Ca2+/calmodulin antagonistic properties is supported by the present study.