Using a test system of graft-versus-host reaction (GVHR) in F1hybrid mice (A/J X C57BL/6J) initiated by the inoculation of neonatal F1mice with parental strain spleen cells, the following conclusions are made in relation to the modification of the GVHR by 6-mercaptopurine (6-MP). 1. 6-MP in total dose of 120 mg/kg body weight or more given over a 6-day period results in splenic hypoplasia in neonatal mice. 2. 6-MP in total dose of 90 mg/kg body weight or less does not result in splenic hypoplasia. 3. The incidence of runt disease is 82% (0.99 confidence limits of 69–91%) in the above strain combination. 4. 6-MP treatment in total dose of 60 to 90 mg/kg body weight reduces this incidence to 55% (0.99 confidence limits of 43–67%). 5. The GVHR may be used as a test system in screening drugs for their effectiveness in altering the immunologic response to allogeneic homografts.