Major histocompatibility complex (MHC) class II molecules are expressed in a limited number of cell types, including B lymphocytes, dendritic cells and macrophages. Lipopolysaccharide (LPS) increases the surface expression of class II molecules in a murine B-cell line by inducing an increase in I-A protein and I-A mRNA levels. LPS does not modify the rate of mRNA degradation; therefore, the increase in mRNA is due to an increase in transcription. In addition, LPS increases the levels of I-A alpha protein, which correlates with an increase in ribosome loading for I-A alpha but not for I-A beta mRNA after treatment with LPS. Interestingly, in non-induced cells, I-A alpha messenger RNA shows a significant peak of free mRNA. Therefore, LPS regulates the expression of MHC class II molecules at translational lever in B cells, in addition to the transcriptional control. The actual mechanism implies changes of translation initiation rates, as shown by an increase ribosome loading in polysome gradients.