1. The hyperpolarization of the resting membrane potential, Vm, induced by isoprenaline in the lumbrical muscle fibres of the mouse, was investigated by use of intracellular microelectrodes. 2. In normal Krebs-Henseleit solution (potassium concentration: K+o = 5.7 mM, 'control'), Vm was -7.40 +/- 0.2 mV; lowering K+o to 0.76 mM ('low K+o') resulted in either a hyperpolarization (Vm = -95.7 +/- 2.9 mV), or a depolarization (Vm = -52.0 +/- 0.3 mV). 3. Isoprenaline (> or = 200 nM) induced a hyperpolarization of Vm by delta Vm = -5.6 +/- 0.4 mV in control solution. 4. When Vm hyperpolarized after switching to low K+o, the addition of isoprenaline resulted in increased hyperpolarization Vm: delta Vm = -16.3 +/- 3.2 mV to a final Vm = -110.1 +/- 3.4 mV. Adding iso-prenaline when Vm depolarized in low K+o, leads to a hyperpolarization of either by -11.6 +/- 0.5 mV to -63.6 +/- 0.8 mV or by -51.7 +/- 2.7 mV to -106.9 +/- 3.9 mV. 5. Ouabain (0.1 to 1 mM) did not suppress the hyperpolarization by isoprenaline in 5.7 mM K+o (delta Vm = -6.7 +/- 0.4 mV) or the hyperpolarization of the depolarized cells in low K+- (delta Vm = -9.7 +/- 1.5 mV). 6. The hyperpolarization is a logarithmically decreasing function of K+o in the range between 2 and 20 mM (12 mV/decade). 7.IBMX and 8Br-cyclic AMP mimicked the response to isoprenaline whereas forskolin (FSK) induced in low K+o a hyperpolarization of -7.0 +/- 0.7 mV that could be augmented by addition of isoprenaline (delta Vm = -8.2 +/- 1.8 mV). 8. In control and low K+o, Ba2+ (0.6 mM) inhibited the hyperpolarization induced by isoprenaline, IBMX or 8Br-cyclic AMP. Other blockers of the potassium conductance such as TEA (5 mM) and apamin (0.4 microM) had no effect. 9. We conclude that in the lumbrical muscle of the mouse the isoprenaline-induced hyperpolarization is primarily due to an increase in potassium permeability.