The pleiotropic cytokine interleukin-6 (IL-6) induces acute phase protein expression in HepG2 human hepatoma cells and promotes the growth of mouse B9 hybridoma. The signaling cascades leading to these biological functions are only partially known. We analysed the involvement of MAPK homologues in IL-6 transduction pathways and found that interleukin-6 triggered activation of p38 stress-activated protein kinase (p38) but not of jun kinase. p38 activity was required for biological functions including acute phase protein secretion from HepG2 hepatoma and proliferation of B9 hybridoma cells. Using a reporter gene construct containing a 190 bp promoter fragment of the acute phase protein haptoglobin we found that p38 is involved in transcriptional activation of the haptoglobin promoter by STAT3 but not by NF-IL6. Thus, we present evidence for a role of p38 in IL-6 induced functions and a possible cross-talk between this MAPK homologue and the STAT pathway.