The sensitivity to anticonvulsants and anesthetics of Ca2+ currents arising from α1G and α1H subunits was examined in stably transfected HEK293 cells. For comparison, in some cases blocking effects on dorsal root ganglion (DRG) T currents were also examined under identical ionic conditions. The anticonvulsant, phenytoin, which partially blocks DRG T current, blocked α1G current completely but with weaker affinity (~140 μM). Among different cells, α1H current exhibited either of two responses to phenytoin. In one subpopulation of cells, phenytoin produced a partial, higher affinity block (IC50 ~7.2 μM, maximum block ~43%) similar to that in DRG neurons. In other cells, phenytoin produced complete, but lower affinity, blockade (IC50 ~138 μM, maximum block ~89%). Another anticonvulsant, α-methyl- α-phenylsuccinimide (MPS), blocked DRG current partially, but blocked both α1G and α1H currents completely with weaker affinity ~1.7 mM). These data suggest that higher affinity blockade of T-type currents by phenytoin and MPS may require additional regulatory factors that can contribute to native T- type channels. In contrast, anesthetics blocked all T current variants similarly and completely. Block of α1G current by anesthetics had the following order of potency propofol (IC50 ~20.5 μM) > etomidate (~161 μM) = octanol (~160 μM) > isoflurane (~277 μM) > ketamine (~1.2 mM), comparable with results on DRG T currents. Barbiturates completely blocked α1G currents with potency [thiopental (~280 μM), pentobarbital (~310 μM), phenobarbital (~1.54 mM)] similar to that in DRG cells. The effects of propofol, octanol, and pentobarbital on α1H currents were indistinguishable from effects on α1G currents.