A new mutant of Paramecium tetraurelia has been isolated with a profound defect in the regulation of membrane potential. This mutant, restless, hyperpolarizes as a potassium electrode below 8 mM external K+ whereas wild-type cells can maintain a constant resting cell potential independent of low external K+ concentration. restless dies in solutions of low K+ concentration in which wild-type can survive indefinitely. restless is not allelic to mutations that affect the depolarization-dependent Ca2+ current, the Ca2+-activated K+ current, and the Ca2+-activated Na+ current. The results suggest that restless is a new class of mutant affecting a K+ conductance hitherto not characterized genetically in Paramecium.