1. The effect of the lanthanide cation Gd3+ on voltage-dependent calcium currents in neuroblastoma x glioma (NG108-15) cells has been studied using a whole-cell clamp technique. 2. Gd3+ reduced the amplitude of calcium currents. The amount of inhibition produced by Gd3+ was concentration dependent between about 0.5 and 5 microM and reached a maximum at about 10-20 microM. 3. A proportion of the total calcium current was resistant to blockade by Gd3+. 4. Gd3+-resistant calcium current consisted of two components: a rapidly inactivating, 'fast' component which was activated at potentials more positive than about -45 mV, and a long-lasting, 'slow' component which was activated at potentials more positive than about -10 mV. 5. It was possible to isolate the slow component, in the presence of Gd3+, by selectively inactivating the fast component with a brief depolarizing pre-pulse. The fast and slow components of current probably reflect the activity of two subpopulations of calcium channels which are resistant to block by Gd3+. 6. In control conditions inactivation of calcium current could be described by the sum of a fast (tau congruent to 40 ms at +10 mV) and a slow (tau congruent to 800 ms at +10 mV) exponential decay plus a constant. Gd3+ selectively blocked the slowly decaying current. 7. The current blocked by Gd3+ was activated at potentials more positive than about -35 mV and decayed monoexponentially (tau congruent to 800 ms at +10 mV). 8. It is concluded that under the experimental conditions used in the present study calcium currents recorded in NG108-15 cells are made up of at least three components which reflect the activity of three distinct subpopulations of calcium channels, one of which is selectively blocked by Gd3+.