Isolation rearing is a developmentally specific non-pharmacological manipulation in rats that produces a deficit in sensorimotor gating, as measured by prepulse inhibition (PPI) of the startle reflex. Previous research has demonstrated that the isolation rearing effect on PPI is sensitive to several factors, including the time of testing with respect to length of isolation, prepulse intensities used, strain of rats, and type of housing environment. This study tested whether handling is another factor that interacts with the isolation-rearing paradigm in PPI. Rats were housed either in the social (three rats per cage) or isolate (one rat per cage) conditions and were handled either 1-2 times per week (minimal handling) or on a daily basis (daily handling). All rats were then tested at 8 and 10 weeks post-weaning. There was an interaction between housing and handling. In the minimal handling condition, isolation rearing produced a deficit in PPI. This effect was absent, however, in the daily handling condition. Thus, regular handling of rats may interfere with the observation of the isolation rearing effect on PPI and should be carefully controlled in studies using this animal model of PPI deficits.