We localized the third (C3) and fourth (C4) components of complement by light and electron microscopic immunocytochemistry in liver biopsy specimens from patients without overt liver disease or with chronic hepatitis. In both groups it was found that almost all hepatocytes contained the two complement proteins in protein-generating organelles, i.e., the perinuclear spaces, cisternae of the rough endoplasmic reticulum, Golgi apparatus, and cytoplasmic transport vesicles. In addition, the sinusoidal membrane and vesicles that appeared to be fused with the membrane were positive for C3 and C4. The complement proteins were absent from the protein-synthesizing apparatus of other kinds of cells, but they were present in phagosomes of Kupffer cells. We conclude that hepatocytes but not other cells in the human liver synthesize C3 and C4. In addition, a plausible pathway for transport of the complement proteins from hepatocytes into the blood circulation was identified.