Neurofibrillary tangles, one of the major pathological hallmarks of Alzheimer‐diseased brains, consist primarily of aggregated paired helical filaments (PHFs) of hyperphosphorylated τ protein. τ from normal brain and especially from foetal brain is also phosphorylated on some of the sites phosphorylated in PHFs, mainly at serines or threonines followed by prolines. A number of protein kinases can phosphorylate τ in vitro; those that require or accept prolines include GSK3 and members of the mitogen‐activated protein (MAP) kinase family, ERK1, ERK2, and SAP kinase‐β/JNK. In this report, we show that another member of the MAP kinase family, the stress‐activated kinase p38/RK, can phosphorylate τ in vitro. Western blots with phosphorylation‐sensitive antibodies showed that p38, like ERK2 and SAP kinase‐β/JNK, phosphorylated τ at sites found phosphorylated physiologically (Thr181, Ser202, Thr205, and Ser396) and also at Ser422, which is phosphorylated in neurofibrillary tangles but not in normal adult or foetal brain. These findings support the possibility that cellular stress might contribute to τ hyperphosphorylation during the formation of PHFs, and hence, to the development of τ pathology.