The C-terminal regions of Kv1 K+ channels show little conservation between isoforms except for the last four C-terminal residues, (E/L)TDV, which are well conserved from Drosophila to man. Deletions of the 4, 16, and 57 C-terminal residues of the human Kv1.5 channel did not affect whole cell current amplitude, midpoint of activation, degree of inactivation, or activation kinetics following expression in mouse L-cells. Similar results were obtained with the rat Kv1.1 channel. Therefore, the conserved (E/L)TDV motif, and most of the C-terminal amino acids, are not required for Kv1 channel expression.