Excitability of intracellularly perfused squid giant axons was maintained in hypotonic solutions (down to 300 mOSM) and in hypertonic solutions (up to about 10 OSM), when osmolalities of internal and external solutions were adjusted to be equal with glycerol, glucose, or sucrose. Molar concentrations of ions were kept constant during one series of experiments. The resting potential and the amplitude of the action potential did not change in both hypotonic and hypertonic solutions. With reduction of osmolality, the duration of action potential decreased and the maximum rate of rise and conduction velocity increased. By raising osmolality, the duration was prolonged and the maximum rate of rise and the conduction velocity decreased. Effects of osmolality change were almost reversible. However, these effects were not directly related to the osmolality change but seemed to be related to the viscosity change of the solutions. When the osmolality of external solution was raised with NaCl (up to 2.6 M NaCl), the overshoot increased in proportion to the logarithm of the NaCl concentration. The slope of increase was about 50 mV/decade. However, the resting potential showed little change. With increase of the NaCl concentration, the duration of the action potential increased.Physiological experiment with nerves are usually performed in isotonic solutions. An osmolality change in bathing solutions around intact nerves is thought to have some effect on nerves, mainly due to an inflow or an outflow of water across the membrane accompanied with a volume change of cells. Use of isotonic solutions alone limits the range of ionic concentration changes that can be made. Until now, many investigators have examined the excitability of nerves (MULLER-MOHNSSEN and BARSKE, 1974) or muscle (HODGKIN and HOROWICZ, 1957;KAWATA et al., 1974;SUAREZ-KURTZ and SORENSON, 1977) in hypotonic and hypertonic solutions. Since they used intact cells, it was difficult to separate the effect of the intended ionic concentration changes from those of changes in cell volume, in cell surface area and in ionic concentrations inside the cell (FREEMAN et al., 1966;