We have previously described a passive serum therapy system in which potent protection against challenge of syngeneic mice with large doses (10(4) X LD100) of AD755a tumor cells can be accomplished by administration of as little as 2 to 5 microliters/mouse of hyperimmune anti-tumor cell serum. The present results demonstrate that the efficacy of the serum protection effect is strain-dependent and is under the control of a single genetic locus, denoted ADP-1. Through a series of crosses between highly protected C57BL/6J and nonprotected BALB/cJ mice, the ADP-locus has been mapped to chromosome 2 [linkage group V], approximately 23 centimorgans toward te centromere from the locus controlling agouti coat color. Thus, the protection locus is not linked to either the H-2 region or to previously described loci regulating the replication and disease induction of type-C viruses closely related to the virus associated with the AD775a tumor. The possible functions of the ADP-1 locus are discussed and further aspects of this experimental model are described in the accompanying papers.