Human peripheral blood lymphocytes (PBL) form E rosettes with sheep red blood cells (SRBC) which tend to disintegrate upon incubation at 37°C and which can be disrupted easily by shaking. Neuraminidase treatment of either PBL or SRBC was found to increase the proportion of stable rosettes resistant to prolonged incubation at 37°C and to vigorous shaking. The proportion of stable rosettes formed was related to the concentration of neuraminidase used. SRBC had to be exposed to higher concentrations of neuraminidase than PBL for the production of stable rosettes. Incubation of PBL with absorbed rabbit antiserum to human thymus (RAHT) completely prevented the formation of either stable or regular E rosettes. Rabbit antisera to human bone marrow or brain had no such effect. The concentration of RAHT required for the inhibition of rosette formation by neuraminidase-treated SRBC or PBL was higher than that required for the inhibition of rosette formation by untreated cells. It is suggested that neuraminidase does not “unmask” receptor sites on either SRBC or PBL, but rather reduces the electric surface charge of the cells, thereby enabling a more effective interaction between receptors exposed on the membrane of PBL and sites on SRBC.