Platelet‐derived growth factor (PDGF) BB is a potent mitogen for renal mesangial cells and stimulates a biphasic mitogen‐activated protein kinase (MAP kinase) activation. A rapid increase in activity (maximal at 10 min) is followed by a lower persistent level of activity which is maximal at 4–6 h. The second peak of MAP kinase activity is markedly attenuated by the protein synthesis inhibitor cycloheximide and, consequently, is paralleled by a marked de‐novo synthesis of p42 and p44 MAP kinases, as measured by immunoprecipitation of [³⁵S]methionine‐labeled mesangial cells and by a 700 % increase in total MAP kinase protein, as detected by Western‐blot analysis. A 30‐min treatment with PDGF‐BB is sufficient to induce pronounced de‐novo synthesis of MAP kinase. However, for maximal induction of MAP kinase synthesis, PDGF is required to be present for at least 4 h. In addition, an increased de‐novo synthesis of MAP kinase kinase, the upstream activator of MAP kinase, is observed in response to PDGF stimulation. We propose that PDGF‐induced de‐novo synthesis of MAP kinase and MAP kinase kinase is important for the potent mitogenic activity of this growth factor.