Activation of mouse lymphocytes with Con A in the presence or absence of serum in the culture medium and the effect of two polymers, PVP and CS, on this stimulation was investigated. The presence of different sera in the culture medium resulted in a different degree of lymphocyte activation and the tested polymers affected it mildly, whereas in serum-free medium they had a strong inhibitory effect. This inhibition was not the outcome of a toxic effect nor of a reduced mitogen-binding capacity of Con A. In investigating the delayed agglutination of lymphocytes with small doses of Con A in vitro, it was found that PVP had a potentiating effect on agglutination in the presence of serum in the medium and an inhibitory effect in serum-free medium. The differences in the action of the tested polymers on stimulation and agglutination of cells in the presence and absence of serum in the medium in vitro suggest a pronounced effect of the sera on cultured cells. The results are discussed with respect to the effect of culture medium on the properties of the lymphoid cell membranes.