Human immunodeficiency virus type 1 (HIV-1) infection is often accompanied by cognitive, motor, and behavioral dysfunction. Cognitive function diminishes in indices of attention, psychomotor speed, and learning and memory. These are collectively termed acquired immunodeficiency syndrome dementia complex (ADC or neuroAIDS). Inoculation with the LP-BM5 murine leukemia virus (MuLV) causes profound immunosuppression (murine acquired immunodeficiency syndrome, or MAIDS) in C57BL/6 mice. Previous studies show that the LP-BM5 MuLV impairs learning and memory without gross motor impairment. Since learning and memory performance deficits can be related to attention deficits, we assessed the effect of LP-BM5 MuLV infection on sustained attention performance using a two-choice serial reaction time task. This task required the animals to detect a visual stimulus presented randomly on the right or the left unit and respond by a nose-poke in the illuminated hole within a 5 s period for water reward. The LP-BM5 MuLV infected group, like the control group, improved sustained attention performance until 7 weeks of virus infection in all measures including choice accuracy, response omission, and correct response time. However, during the late stage of infection, LP-BM5 MuLV infected mice showed selective sustained attention performance deficits. From 8 weeks after LP-BM5 MuLV infection, the virus infected mice started to lose their improved sustained attention performance in response omission and began to make correct responses more slowly than the control mice when the duration of stimulus light was 5 s. Moreover, at 13 and 14 weeks after LP-BM5 MuLV infection, the virus infected group made correct choices significantly less accurately than the control group when duration of stimulus light was shortest (1 s). These data show that LP-BM5 MuLV infection causes not only the previously reported learning and memory deficits but also produces sustained attention performance deficits in mice.