Affinity maturation by somatic hypermutation is thought to occur within germinal centres. Mice deficient in lymphotoxin-α (LTα(-/-) mice) have no lymph nodes or Peyer's patches, and fail to form germinal centres in the spleen. We tested whether germinal centres are essential for maturation of antibody responses to T-cell-dependent antigens. LTα(-/-) mice immunized with low doses of (4-hydroxy-3-nitrophenyl)acetyl-ovalbumin (NP-OVA) showed dramatically impaired production of high-affinity anti-NP IgG1. However, LTα(-/-) mice immunized with high doses of NP-OVA, even though they failed to produce germinal centres, manifested a high-affinity anti-NP IgG1 response similar to wild-type mice. Furthermore, when LTα(-/-) mice were multiply immunized with high doses of NP-OVA, the predominantly expressed anti-NP VH gene segment VHI86.2 showed somatic mutations typical of affinity maturation. Thus, B-cell memory and affinity maturation are not absolutely dependent on the presence of germinal centres.