To investigate the role of sIa in B lymphocyte development, mice were injected from birth with hybridoma anti-Ia antibody. There was on the average a 95% reduction in the number of sIgD+ cells, and 85% diminution in the number of sIgM+ cells, a small but significant increase in the number of sIgM+ sIgD- sla- B cells, as well as a dramatic increase in the number of sIgM- cells bearing a B lineage antigen. Exposure of cells to high doses of anti-Ia antibody in vitro or in vivo for 24 hr did not affect the number of sIg+ lymphocytes. Thus, it appears that chronic anti-Ia administration critically alters normal B lymphocyte development.