Abstract We studied whether serum basic proteins (BPs) produce abnormal changes in the mass of cellular lipids in fibroblasts from patients with hyperapobetalipoproteinemia (hyperapoB) and if inhibition or stimulation of protein kinase C affects these processes. In normal cells, BP I increased the mean mass of triglycerides about twofold, whereas there was significantly less stimulation in hyperapoB cells (P<.005). The increase in the mass of cell cholesteryl esters seen in normal cells with BP I was also significantly reduced in hyperapoB cells (P<.005). In contrast, BP II abnormally stimulated the mass of cell cholesteryl esters sixfold in hyperapoB cells (P<.005). BP I also stimulated the mass of total phospholipids about twofold in normal cells, an effect that was reduced by about one third in hyperapoB cells (P=.08). No abnormality was found in hyperapoB cells with BP III. H-7, an inhibitor of protein kinase C, decreased the effects of BP I and BP II in normal and hyperapoB cells. C:8, an analogue of diacylglycerol, activated protein kinase C and stimulated triglyceride formation in normal (fourfold) and hyperapoB (fivefold) cells in the absence of BP I. When added with C:8, BP I further increased triglyceride production 1.5-fold in normal cells but not in hyperapoB cells. Two cellular abnormalities in lipid metabolism in hyperapoB fibroblasts were found, one with BP I, another with BP II. Protein kinase C activity was not deficient in hyperapoB cells, and the defect(s) may occur at another, perhaps earlier, step in the pathway.