Studies on model phospholipid membranes have shown that general anesthetics and pressure exert opposing effects--anesthetics increase and high pressure decreases membrane fluidity. The present study extends these investigations to intact nerve membranes. The fluidity of the membranes of spin-labeled crayfish claw nerves was measured with electron paramagnetic resonance spectroscopy. Nerves exposed to 5- or 10% ethanol showed a linear increase in membrane fluidity. In contrast, 100 ATA of helium pressure decreased nerve fluidity. Successive application of ethanol and pressure to the nerve produced opposing effects. The similarity of effects between model and nerve membranes supports the relevance of studies with model systems.