The effects of high K(+) exposure on the accumulation of diacylglycerol (DAG) and on the activation of protein kinase C (PKC) have been studied in frog skeletal muscle. The endogenous DAG increased by treatment with 80 mM K(+) for different lengths of time. Correspondingly, high K(+) exposure could induce a translocation of PKC. For instance, The membrane-associated PKC activity (pmol/min.g muscle) was increased from the control value of 523mmplus;37 to 725mmplus;33 and 858mmplus;59 after 80 mM K(+) exposure for 2 and 60 minutes, while the cytosolic PKC activity was reduced from 543mmplus;35 to 307mmplus; mmplus;20 and 254mmplus;46, respectively. The accumulation of DAG and the activation of PKC induced by high K(+) exposure suggest a possible role of the pathway of DAG/PKC in the regulation of the excitation-contraction coupling in skeletal muscle fibres.