When heat-killed, cultured human kidney cells were incubated with normal human serum, complement (C) activation occurred with moderate consumption of C4, C2, C3, and C5 hemolytic activity. No loss of C1 activity and no, or only slight, reduction in C6 activity was detectable until high cell concentrations were reached. C4 and C2 consumption could not be prevented by blocking the primary C pathway through prior EGTA chelation of the serum. Both living and heat-killed kidney cells were incubated with normal serum and examined for surface-bound C components using immunofluorescent techniques. Heat-killed kidney cells were strongly positive for C3, which was distributed in a diffuse, speckled pattern over the entire cell surface. These cells were also weakly positive for IgG and Clq immunofluorescence, but were negative for surface albumin, C5, and beta 1H. In contrast, living cell suspensions showed only occasional cells positive for C3, IgG, or Clq and all cells were negative for albumin, C5, and beta 1H. Viability staining revealed that the few C3 positive cells in living cell suspensions belonged to a small, nonviable subpopulation. These data indicate that dead cells can initiate limited C activation, which can result in binding of C3 to the cell surface.