We have verified the consequences of alterations of the lipidic phase of HEp 2 cell membranes on susceptibility to infection from Herpes simplex virus, and have related these results to modification in membrane fluidity. This was carried out by treating HEp 2 cells with saturated and unsaturated fatty acids with chain lengths from eight to 18 carbon atoms. The results show that HEp 2 cells treated with saturated fatty acids with eight and ten carbon atoms have both increased membrane fluidity and increased susceptibility to Herpes simplex virus infection while both parameters were reduced when HEp 2 cells were treated with saturated fatty acids having 14 and 18 carbon atoms. Fatty acids with 16 carbon atoms, however, show an increase in membrane fluidity which has no significant correlation to infection susceptibility. As to unsaturated acids, those with eight carbon atoms, 2-octenoic acid (trans-8: 1[2]) and 2-octynoic acid (8:::1[2]), increase the susceptibility to infection and fluidity while low concentrations of monounsaturated acids with 14 and 18 carbon atoms, myristoleic acid (cis-14:1[9]) and oleic acid (cis-18:1[9]), reduce both the susceptibility to infection and the fluidity of the membrane.