Protein kinase C (PKC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonic resection. Comparisons were made between cases with and without colorectal cancers. PKC activity in cytosolic and particulate fractions was significantly reduced in patients with colorectal cancer: 40 +/- 9 and 114 +/- 29 (pmol/min/mg) respectively, compared with patients without cancer; 129 +/- 11 and 250 +/- 38 (pmol/min/mg) (p less than 0.05). Normal-appearing colonic mucosa in patients with cancer showed significantly decreased total PKC activities in the cytosolic and particulate fractions compared with those in patients without cancer (10 +/- 1 and 20 +/- 3 vs. 30 +/- 2 and 33 +/- 6) (pmol/min/g tissue) (p less than 0.05). The cellular distribution (% particulate fraction) of PKC activity in normal-appearing mucosa in patients with cancer (64%) was higher than in patients without cancer (49%) (p less than 0.05). OUr data suggest that PKC activity may be used as a biological marker of risk of developing colorectal cancer or risk of bearing an asymptomatic tumor.