Trichostatin A (TSA) is a potent reversible inhibitor of histone deacetylase, and it has been reported to have variable effects on the expression of a number of genes. In this report, we show that TSA suppresses the expression of the T cell receptor ζ chain gene, whereas, it upregulates the expression if its homologous gene Fcε receptor I γ chain. These effects are associated with decreased intracytoplasmic‐free calcium responses and altered tyrosine phosphorylation pattern of cytosolic proteins. Along with these effects, we report that TSA suppresses the expression of the interleukin‐2 gene. The effects of TSA on human T cells are predominantly immunosuppressive and reminiscent of the signaling aberrations that have been described in patients with systemic lupus erythematosus. J. Cell. Biochem. 85: 459–469, 2002. Published 2002 Wiley‐Liss, Inc.