Hind footpads of mice of inbred strains were injected with horseradish peroxidase (PO) in Freund's complete adjuvant (FCA) and the response of the antibody-forming cells (AFC) in their popliteal lymph nodes was measured. Marked strain differences were found after the first injection and three types of responder strains were defined: high responders, with H-2(s), H-2(a) and H-2(b) haplotypes, low responders, with the H-2(d) haplotype and an intermediate type of responder, observed in mice of the H-2(k) and H-2(q) haplotypes. After a second injection of PO in FCA, strain differences in the response disappeared and all strains responded equally well. F(1) hybrids from high and intermediate or low responders gave a mean AFC response between the two parental responses. Immunoglobulin-forming cells (IFC) with no anti-PO function, appearing concomitantly with AFC in PO+FCA-immunized mice, were also counted. Compared with the IFC found in mice given FCA only, their number was always higher (two-five times more). The IFC response followed the same pattern as the AFC response and was high, intermediate and low in high, intermediate and low responders, respectively. The IFC:AFC ratio varied depending on how many days after the challenge it was measured, but was similar for all strains except the low responder strains, in which the ratio remained constant at approximately 1 throughout the immune response. Like the AFC response, the IFC counts in F(1) hybrids gave intermediate values, except in hybrids from the two low responders (BALB/c and DBA/2) in which there were five times more IFC than AFC. We concluded that PO responsiveness in mice seems to be under genetic control governed by the H-2 locus and by non-H-2 genes and that the IFC which appear concomitantly with AFC are under the same genetic control
