An inactivated virus vaccine was developed for prevention of FeLV infection in domestic cats. When given in 2 doses, 3 weeks apart, to cats that were greater than or equal to 9 weeks old at the time of first vaccination, the vaccine prevented persistent viremia from developing in 132 of 144 (92%) vaccinates after oronasal challenge exposure with virulent FeLV. In contrast, persistent viremia developed after oronasal challenge exposure with FeLV in 39 of 45 (87%) age-matched nonvaccinated control cats. Transient viremia, indicated by early detection of p27 by ELISA in serum of cats protected from persistent viremia at 12 weeks after challenge exposure, was found in 10 of 132 (8%) vaccinates. Cats that were aviremic 12 to 16 weeks after challenge exposure were examined for reactivation of latent FeLV infection; 4 weekly doses of methylprednisolone were administered, followed by in vitro culture of bone marrow cells. Latent infection was readily reactivated in 6 of 8 (75%) nonvaccinated control cats that had been transiently viremic after challenge exposure. However, latent infection was reactivated in only 5 of 48 (10%) protected vaccinates, and in none of 38 vaccinates in which transient viremia had not been detected. In a safety field trial, only 34 mild reactions of short duration were observed after administration of 2,379 doses of vaccine to cats of various ages, breeds, and vaccination history, for a 1.43% reaction rate. Results indicate that the aforementioned inactivated virus vaccine is safe and efficacious for the prevention of infection with FeLV.