A/Jax and C57BL/6J neonatal mice which received allografts of neonatal skin reciprocally as early as the day of birth were found to reject such grafts vigorously with median survival times only slightly longer than those determined for adult allograft rejection. Preimmuni-zation with 200,000 allogeneic adult thymocytes as early as the day of birth consistently led to accelerated rejection of test skin allografts placed 4 days later, while preimmunization with 50,000 cells led to accelerated rejection in about half of the neonatal recipients similarly tested. BL/6 mice older than 5–8 days rejected large doses of A/J tumor cells (Sarcoma I), whereas younger mice were killed by progressive tumor growth. However, preimmunization with 200,000 A/J thymocytes effectively protected BL/6 neonates against an inoculum of 100,000 tumor cells injected 4 days later. Maturation of the allohemag-glutinin response in BL/6 mice to a variety of A/J thymocyte dosages was demonstrated at about 11 days of age. In contrast, A/J mice first showed allohemagglutinin production at 17–23 days of age and high doses of BL/6 adult thymocytes often led to unresponsiveness. Early antibodies in representative immune serums from neonatal and juvenile mice were separated by Sephadex G-200 fractionation and then characterized by analytical ultracentrifugation in conjunction with hemagglutination tests. Antibodies detected prior to 20 and 27 days of age in BL/6 and A/J mice, respectively, were solely macroglobulins sedimenting at 20.3–20.8S. However, older mice of either strain produced 7S gamma-globulin sedimenting at 6.5–6.8S, in addition to macroglobulins. The data substantiate and extend previous observations of transplantation immunity in neonatal mice, and demonstrate that 19S and 7S-type antibodies induced by allogeneic antigens follow the general maturation sequence of antibody types to xenogeneic antigens described for other species. Maximal transplantation immunity was inducible in neonates long before macroglobulin allo-hemagglutinins were detectable under diverse tactics of immunization.