Sarcoma 180 (S-180) grows in 0–10% of AKR mice. The incidence of tumor growth is increased in animals implanted 3 weeks previously with another graft of this tumor. This increase in incidence of growth is prevented by splenectomy. Similarly, treatments with frozen-thawed homogenates of S-180 greatly increase the incidence of growth of S-180 in sham-operated but not in splenectomized AKR mice. The growth of adenocarcinoma 755, sarcoma I, leukemia L 1210, and an adenocarcinoma of C3H origin is not promoted by this treatment. Conversely, the administration of homogenates of Walker carcinoma 256, adenocarcinoma 755, and spleen and liver of C57BL/ 6/Ja, DBA/2Ha, or Swiss/HaICR mice does not promote the growth of S-180. S-180 frozen-thawed homogenates treated at 57 C for 30 min are only slightly less effective than nontreated S-180 frozen-thawed homogenates. These data indicate that active immunological enhancement is responsible for the observed increase of S-180 growth in AKR mice and that the spleen plays an important role in it.