Interleukin-1 (IL-1) stimulates a time- and concentration-dependent mitogen-activated protein (MAP) kinase activation in rat mesangial cells. A rapid increase in activity (maximal at 10 min) is followed by a second persistent level of activity which steadily increases over 24 h. The second peak of MAP kinase activity is paralleled by a marked de novo synthesis of p42 MAP kinase as measured by immunoprecipitation of [35S]methionine-labelled mesangial cells and by a 60% increase in total p42 MAP kinase protein as detected by Western blot analysis. We propose that IL-1 induced de novo synthesis of p42 MAP kinase is important for the multiplicity of long-term actions of this cytokine in renal mesangial cells.