A monoclonal antibody, M522, reacting with human monocytes, neutrophils and a proportion of non-adherent PBL in a pattern similar to OKM-1 and anti-Mo-1, and precipitating a dimer of MW 165,000 and 100,000 from neutrophils, was shown to react with C3 at an epitope localized on the alpha-chain of C3. F(ab)2-fragments of M522 stimulate the respiratory burst of neutrophils and monocytes. M522 differs from two monoclonal antibodies against the Mo-1 molecule with respect to the capacity to inhibit the binding of sheep erythrocytes coated with different C3-fragments to C-receptor carrying cells. It inhibited the binding of H-coated particles to B-lymphoid cells and precipitated a 50,000 MW molecule from RAJI cells and tonsil lymphocytes. The results obtained suggest an antigenic relationship between the alpha-chain of C3, the heavy chain of a membrane molecule involved in neutrophil/monocyte activation, and a B-cell molecule of MW 50,000.