The effects of ev6, ev21, sex, and hatch, were studied with respect to avian leukosis virus (ALV) viremia, cloacal shedding, and antibody response among RPL-40 virus-infected White Leghorns that carried ev6 and ev21 in all combinations. Among the four possible ev genotypes, chickens that carried only ev21 were the most immunologically tolerant to RPL-40 infection. Incidence of RPL-40 viremia was lowest among hatchmates that lacked both ev genes. Analysis of variance indicated significant interactions between ev6 and ev21 with respect to all responses. Among ev21+ slow-feathering (SF) chickens, the incidence of viremia and shedding of RPL-40 was reduced in the presence of ev6 when compared with ev6- hatchmates. Conversely, among ev21- rapid-feathering (RF) chickens, ev6 significantly enhanced the incidence of RPL-40 viremia when compared with ev6- hatchmates. The endogenous virus, ev6, markedly reduced recovery of the endogenous virus (EV21) from plasmas of slow-feathering chickens. When both flocks were terminated at 21 wk of age, significantly more ev21+ SF females had died from or developed RPL-40-induced tumors than ev21- hatchmates.