Addition of phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC) to cultured glial cells increased the levels of nerve growth factor (NGF) mRNA and the amount of cell-secreted NGF, The effect of PC-PLC was 2.5 times higher than that elicited by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate. In cells in which protein kinase C (PKC) was fully inhibited or downregulated, the effect of PC-PLC was reduced - though still evident - and similar to that exerted by sphingosine. Results thus indicate that PC-PLC induces the synthesis of NGF by glial cells by a PKC-dependent and PKC-independent mechanisms.