Injection of a hybridoma anti-Ia antibody into adult mice results in a dramatic reduction in the expression of B cell sIa without affecting the expression of sIgD or sIgM. This anti-Ia-mediated modulation of B cell sIa occurs within 3 hr and attains it maximum effect within 18 hr after injection of antibody. There is a rapid reexpression of B cell Ia when such sIa- B cells are cultured in vitro. Culture of B cells in vitro with anti-Ia antibody has no discernible effect on the expression of B cell sIa, nor does it prevent the reexpression of sIa on sIa- B cells obtained from anti-Ia-injected mice. Injection of anti-I-A antibody suppresses the expression of both I-A and of I-E, and similarly, injection of anti-I-E suppresses the expression of B cell I-E and I-A antigens. When fluorescein-labeled monoclonal anti-I-A antibody is injected into mice, a significant fraction of B cell sIa can be demonstrated to be internalized by the B cell. The potential immunologic significance of this phenomena of anti-Ia-mediated modulation of B cell sIa is discussed.