In most crosses of high-leukemic AKR mice with mice of a low-leukemic strain, mice of the F1 generation show a low and late incidence of spontaneous leukemia. In previous studies we have found that the Fv-1 allele inherited from the low-leukemic parent was responsible for leukemia. We now propose to study other such crosses in which preliminary evidence suggests that a gene other than Fv-1 is responsible. This will be done by observing mice of the F1 x AKR backcross generation for leukemia development and by testing for correlations with Fv-1 type or with other markers segregating in the cross. At the same time we will test whether leukemia is associated with expression of either ecotropic or xenotropic murine leukemia virus in these mice. Other related experiments proposed include an investigation of the basis for ecotropic virus expression in (DBA/2 x RF) F1 mice although this virus is strongly suppressed in both parental strains. We will also study the occurrence of T-cell leukemia vs. Hodgkin's-like lymphoma in crosses of AKR x SJL.