RWJ 67657 is an orally active inhibitor of the MAP kinases p38α and p38β (IC50s = 1 and 11 μM, respectively, in vitro) that is inactive against p38γ and p38δ, as well as several other kinases. It blocks the release of TNF-α and IL-1β from peripheral blood mononuclear cells stimulated with LPS (IC50s = 3 and 11 nM, respectively) and inhibits TNF-α production in LPS-treated mice and rats. RWJ 67657 potently blocks the proliferation of CD4+ peripheral blood T cells induced by CD28 stimulation alone (IC50 = 0.5-4 nM). It is commonly used to study the roles of p38α and p38β in cellular and whole animal systems.