Lymph node cells collected from CBA/J mice 4 days after painting with picryl chloride induce contact sensitivity in naive recipient mice by virtue of hapten IgM immuno complexes. The immunizing capacity of these cells ("4-day" cells) is abolished after incubation of the cells with a C4-deficient guinea pig serum reconstituted with plasma or purified C4 from mice with high C4 levels (C4h), but not with plasma or purified C4 from mice with low C4 levels (C41). The inhibition of the immunizing capacity of 4-day cells is due to the activation of the early components of the classical complement pathway which is likely to result in the solubilization of membrane-bound immunocomplexes. However, the same amounts of CBA/J and BALB/c C4 have a different effect in inhibiting the induction of contact sensitivity by 4-day cells. In fact, by dose-response experiments, we have found that the amount of C41 able to inhibit the induction of contact sensitivity is about threefold higher than that of C4h. Analysis of the covalent binding ability of C4h and C41 reveals that C4h is able to bind to the surface of 4-day cells more efficiently than C41 and this probably accounts for the difference of the two C4 molecules in inhibiting the immunizing capacity of 4-day cells. Results are discussed in terms of different reactivities of C4h and C41 with the surface of 4-day cells.