Pregnant rabbits of the two partially inbred strains III and WH were given ip injections of a single dose of l-ethyl-l-nitrosourea (ENU) (60 mg/kg) in trioctanoin on day 18 of gestation. Controls were treated on the same day with solvent alone. Fourteen of 15 strain III progeny that survived more than 8 weeks developed primary renal tumors at a mean age of 3.3 months. Five other treated strain III progeny died at an early age due to other causes. In contrast, only 3 of 7 strain WH offspring surviving more than 8 weeks developed renal tumors; they had about the same latency period (3.9 months). In each strain, either renal tubular cystadenomas or mixed nephroblastomas appeared to develop within small renal cortical cysts. In strain III, the presence of these cysts may have been due to a high frequency of a recessive gene (rc) for renal cysts, but in strain WH they were induced by ENU. The differential strain incidence suggests that susceptibility to renal tumor inducibility by ENU is increased by the presence of the rc/rc genotype for cyst formation.