Lymphotoxin α (LTα)–deficient mice revealed critical roles for LTα in lymphoid organogenesis, but it is not clear whether LTα functions through an LTα homotrimer (LTα₃) or LTα/β heterotrimers. We generated LTβ-deficient mice and found them to lack Peyer's patches, peripheral lymph nodes, splenic germinal centers, and follicular dendritic cells. Unlike LTα-deficient mice, LTβ-deficient mice had cervical and mesenteric lymph nodes. Furthermore, the mesenteric lymph nodes had germinal center–like regions, although these structures appeared to lack follicular dendritic cells. The absence of cervical and mesenteric lymph nodes in LTα-deficient mice, and yet their presence in LTβ-deficient mice and in mice deficient in tumor necrosis factor receptor types I and II, suggest that LTα₃ may signal via an as yet unidentified receptor.