We have established a gene regulatory system in mice by the inducible anti-sense RNA. We have generated transgenic mice carrying the anti-sense DNA composed of the class II MHC gene under the control of the human metallothionein IIa gene promoter. The detectable amount of anti-sense RNA was constitutively produced in spleen and bone marrow from transgenic mice and the amount in spleen was increased about fivefold by the stimulation of mice with heavy metal ions. We have previously reported that the reduction of class II MHC molecules on early B lineage cells by the anti-sense RNA results in delay of their development in the bone marrow culture. The early B cell development was slightly delayed in the culture from the transgenic mice. This delay was augmented in the culture by the addition of heavy metal ions in proportion to its concentration. These results suggest that the inducible anti-sense RNA reduces the expression of class II MHC molecules on B lineage cells.