The effects of external Rb+ on the efflux of 42K+ from whole frog sartorius muscles loaded with 305 mM K+ and 120 mM Cl- were studied. K+ efflux is activated by [Rb+]o less than about 40 mM according to a sigmoid relation similar to that for activation by [K+]o. At [Rb+]o greater than 40 mM, K+ efflux declines, although at [Rb+]o = 300 mM it is still greater than at [Rb+]o = 0 mM. For low concentrations, the increment in K+ efflux over that in K+-and Rb+-free solution, delta K, is described by the relation delta k = a[X+]on, for both K+ and Rb+. The value of a is larger for Rb+ than for K+, while the values of n are similar; the activation produced by a given [Rb+]o is larger than that by an equal [K+]o for concentrations less than about 40 mM. Adding a small amount of Rb+ to a K+-containing solution has effects on K+ efflux which depend on [K+]o. At low [K+]o, adding Rb+ increases K+ efflux, the effect being greatest near [K+]o = 30 mM and declining at higher [K+]o; at [K+]o above 40 mM, addition of Rb+ decreases K+ efflux. At [K+]o above 75 mM, where K+ efflux is largely activated, Rb+ reduces K+ efflux by a factor b, described by the relation b = 1/(1+c[Rb+]o). Activation is discussed in terms of binding to at least two sites in the membrane, and the reduction in K+ efflux by Rb+ at high [K+]o in terms of association with an additional inhibitory site.