The activity of protein kinase C (PKC) in human liver cancer and adjacent normal liver tissue was determined. It was found that the activity of the membrane-bound PKC was significantly decreased in cancer tissue compared with that of the adjacent normal tissues (245.3 +/- 49.3 versus 396.9 +/- 82.4 pmol 32P/min per mg, P < 0.05); while the PKC activity in the cytosolic fraction was not significantly different (50.6 +/- 11.3 versus 40.0 +/- 6.6 pmol 32P/min per mg) concerning protein concentration. The reduced expression of membrane-bound PKC activity was observed at least in 8 of 9 patients. Moreover, the cancer tissue showed a significant decrease in total membranous PKC activity compared with the adjacent normal tissue of each patient (163.1 +/- 38.8 versus 433.8 +/- 92.4 pmol 32P/min per g tissue; P < 0.005) and no difference in total cytosolic PKC activity (285.9 +/- 58.8 versus 311.6 +/- 44.0 pmol 32P/min per g tissue). These results indicate that the progression of the human liver cancer might be associated with the decrease of membrane-bound PKC activity.