Treatment of GH₃ pituitary cells with p-chloromercurybenzenesulfonate (PCMBS) increased the cytosolic Ca²⁺ concentration ([Ca²⁺]_i). This effect was reversed by dithiothreitol and blocked by L-type Ca²⁺ channel antagonists or Na⁺ removal. PCMBS increased membrane conductance and depolarized the plasma membrane. Apart from minor effects on K⁺ and Ca²⁺ channels, PCMBS increased (6 times at 80 mV) an inward Na⁺ current whose properties were similar to those of a background Na⁺ conductance (BNC) described previously, necessary for generation of spontaneous electrical activity. In rat lactotropes and somatotropes in primary culture, PCMBS also produced a Na⁺-dependent [Ca²⁺]_i increase, whereas little or no effect was observed in thyrotropes, corticotropes, and gonadotropes. The Na⁺ conductance elicited by PCMBS in somatotropes seemed to be the same as that stimulated by the hypothalamic growth hormone (GH)-releasing hormone, which regulates membrane excitability and GH secretion. The BNC studied here could play a physiological role, regulating excitability and spontaneous activity, and explains satisfactorily the [Ca²⁺]_i-increasing actions of the mercurials reported previously in several excitable tissues.