In seeking the putative mechanism of action of diethyldithiocarbamate (DTC) on the immune status of HIV infected patients, the plasma membrane fluidity of peripheral blood lymphocytes (PBL) from DTC-treated and untreated patients (CDC III-IVc1) was determined. Anisotropy values of the fluorescent probe 6-(9-anthroyloxy) stearic acid were increased in DTC-treated patients (0.175 vs 0.161), indicating decreased PBL plasma membrane fluidity. The membrane rigidifying effect was significantly greater 4 h after i.v. drug administration (0.185 in treated patients). As the membrane fluidity and the function of membrane embedded antigen are interdependent, it is possible that alterations in biophysical and/or biochemical properties of membranes may account for the beneficial effect of DTC on the immune function and clinical status of HIV infected patients.