The effects of trifluoperazine (TFP) on basal and stimulated release of prolactin (PRL) and growth hormone (GH) and on the electrical properties of the membrane were studied in clonal rat pituitary tumour cells in culture (GH3 cells). The basal GH release was inhibited maximally 50% by TFP (13-30 microM) and the K+- and thyroliberin (TRH)-induced stimulation of both PRL and GH release was blocked significantly. The sustained depolarization caused by elevated extracellular K+ concentration and the biphasic membrane potential response to TRH (normally leading to spontaneous action potentials) were not affected by TFP. However, TFP inhibited the Ca2+-dependent action potentials, probably by blocking the voltage sensitive Ca2+ channels in the membrane. We therefore suggest that TFP inhibits hormone release by blocking the uptake of extracellular Ca2+. This action of TFP is probably due to direct membrane effects which are independent of calmodulin.