Transgenic mice expressing HIV-1 coat glycoprotein gp120 in brain glial cells were previously shown to display AIDS dementia-like neuropathological changes and reduced hippocampal long-term potentiation. In this report, neuromotor and cognitive performance in 3- and 12-month-old gp120-expressing mice was compared with wildtype controls. Rotarod and cage activity measures showed no significant differences between transgenic animals and controls of either age. Open field activity was slightly altered in 12-month-old gp120 animals (reduced corner crossings and dwell in centre), but not in the 3-month-olds. Cognitive assessment using the Morris water maze showed unimpaired performance in 3-month-old mice during acquisition and (no-platform) probe trials. In 12-month-old gp120 animals, escape latency and swimming velocity during the acquisition trials were significantly reduced, but performance improved at roughly the same rate as in control animals. However, the probe trials revealed a highly significant reduction in spatial retention in transgenic mice of this age. This demonstration of age-dependent impairments in open field activity and spatial reference memory may relate to cognitive and neuromotor deficits seen in a proportion of HIV-1-infected individuals.