A direct in vitro reaction between complement system and cell nuclei of human leucocytes and of cryostat sections of rat liver or kidney, has been demonstrated by an indirect immunofluorescence technique. The first step of this reaction involves a fixation of C1q to the nuclear DNA as shown by the peripheral distribution of the fluorescence and by the extinction of the fluorescence when the tissue-slices are pretreated by DNase but not by RNase or trypsin. This fixation gives rise to an activation of C1 which can be demonstrated by the capacity of the fixed C1 to induce a fixation of C4 of the same distribution. Although the sequential fixation experiments have not allowed to establish directly the fixation of the following components of the complement system (C2 and C3), the positive results obtained using whole fresh normal human serum as a source of complement and a fluorescent anti-human C3 serum clearly indicate that the activation of the classical pathway by whole cells DNA can go as far as the C3 step. All these results were obtained at physiological pH and molarity: this can suggest a physiopathological meaning for this reaction.