Previously the role of invariant chain (ii) had been described only as a chaperone that facilitates folding and transport of major histocompatability complex class II molecules; here it is shown that Ii is required for B cell development. B cells from mice lacking Ii were found to have a low response to T-independent type II antigen and could not proliferate after the mice were injected with antigen. Study of cell surface markers revealed a developmental arrest that prevented immature virgin B cells from becoming mature B cells in the periphery. This block was independent of major histocompatability complex class II expression and was an intrinsic feature of B cells that correlated with the amount of Ii. Thus, Ii participates by an unknown mechanism in B cell maturation.