The expression of the H2 Ia-associated invariant chain (Ii) has been determined by pulse labeling cells with [35S]methionine and resolving the proteins. Expression is maximal in noncycling peripheral B lymphocytes and is reduced upon maturation of B lymphocytes to plasma cells. B cell-derived cell lines behave correspondingly: IgM+ non-secretor cell lines synthesize Ii while plasmocytoma cells do not. Pre-B cell lines are also negative. In all Ii-negative cell lines, the synthesis of Ii is selectively induced by treating the cells with inhibitors of replication.