The antigenic heterogeneity of the reticular framework of the white pulp (WP) and marginal zone (MZ) is well documented in the human adult spleen. The ontogeny of the WP and MZ of human fetal spleens was examined with special reference to the heterogeneity of the reticular framework. In the spleen of the 17th gestational week (gw), alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells were scattered around the arterioles. From the 20th to 23rd gw, alpha-SMA-positive reticulum cells increased in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive WP was observed around the arterioles. At the 24th gw, antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-SMA-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative. MZ appeared in the alpha-SMA-positive reticular framework around the WP at the 26th gw. The PALS, LF, and MZ developed with gestational time. The reticular framework of the PALS, LF, and MZ is thus heterogeneous in the fetal spleen, and the development of the heterogeneity is related to the ontogeny of the PALS, LF, and MZ.