The inhibition of L- and T-type Ca2+ currents by Gd3+ was studied in the rat pituitary GH4C1 cell line. In whole cell patch recordings, Gd3+ at concentrations of 50 nM to 5 microM blocked Ca2+ current through L-type channels. Block was promoted by prolonged channel activation. With 4.5-s test pulses to + 10 mV, Gd3+ at concentrations as low as 200 nM produced near-complete block of L current. At higher Gd3+ concentrations (5 microM), complete block occurred with short test pulses and appeared to be independent of channel activation. Gd3+ also blocked current through low-threshold T channels in GH4C1 cells. Two other trivalent elements, La3+ and Y3+, blocked L-type Ca2+ channels in GH4C1 cells with potency similar to Gd3+. These results indicate that these trivalent cations are effective nonselective inhibitors of both low- and high-threshold Ca2+ channels in endocrine cells. In this regard, they are among the most potent inorganic Ca2+ antagonists yet discovered.