To evaluate the mechanism(s) of erythrocyte stabilization in hypotonic medium by free fatty acids, we have studied the effect of palmitic acid and its derivatives on human erythrocyte membrane electrochemical properties, osmotic stability and fluidity. Palmitic acid increased the membrane potential to the highest extent as compared with its derivatives. The membrane potential was equal to -11.0 +/- 1.7 mV in the absence and -23.3 +/- 3.2 mV in the presence of 400 mumol 1(-1) of palmitic acid, -15.3 +/- 2.2 mV in the presence of 400 mumol 1(-1) of methyl ester of palmitic acid and -14.2 +/- 1.8 mV in the presence of 400 mumol 1(-1) of lauric aldehyde. We propose that free fatty acids, containing the charged carboxylic end group, in contrast to the corresponding esters or aldehydes, can act as ionophores. At the same time, the osmotic stabilization of erythrocytes by palmitic acid and its derivatives was higher in sodium-containing as compared with potassium-containing media and did not correlate with the effect of these compounds on the membrane potential. We suggest that protective potassium leakage does not play a main role in erythrocyte osmotic stabilization by free fatty acids. Possibly this stabilization is due to the structural rearrangement of the whole membrane.