It has been hypothesized that R-type Ca currents result from the expression of the α1(E) gene. To test this hypothesis we examined the properties of voltage-dependent Ca channels in mice in which the α1(E) Ca channel subunit had been deleted. Application of θ-conotoxin GVIA, ω-agatoxin IVA, and nimodipine to cultured cerebellar granule neurons from wild-type mice inhibited components of the whole-cell Ba current, leaving a 'residual' R current with an amplitude of ~30% of the total Ba current. A minor portion of this R current was inhibited by the α1(E)-selective toxin SNX-482, indicating that it resulted from the expression of α1(E). However, the majority of the R current was not inhibited by SNX-482. The SNX-482-sensitive portion of the granule cell R current was absent from α1(E) knock-out mice. We also identified a subpopulation of dorsal root ganglion (DRG) neurons from wild-type mice that expressed an SNX-482-sensitive component of the R current. However as with granule cells, most of the DRG R current was not blocked by SNX-482. We conclude that there exists a component of the R current that results from the expression of the α1(E) Ca channel subunit but that the majority of R currents must result from the expression of other Ca channel α subunits.