Neuropsychiatric manifestations are a poorly understood and potentially life-threatening complication of systemic lupus erythematosus (SLE). MRL/1pr mice spontaneously develop a lupus-like syndrome which is similar to the human disease in many respects, including behavioural abnormalities. Our previous findings indicated that the age at which infiltration of immune cells into the choroid plexus is first observed coincides with the appearance of behavioural dysfunction in MRL/1pr mice. This present study quantified leukocyte infiltration in relation to prolonged administration of cyclophosphamide (CY), a treatment effective in preventing some behavioural deficits. Compared to MRL + / + controls, saline-treated MRL/1pr mice had significantly more CD45-positive cells (leukocytes) and CD45R-positive (B) cells in the choroid plexus and in the brain parenchyma. A six week course of CY (100 mg/kg i.p.) significantly reduced the infiltration of CD45, but not of CD45R-positive cells into the choroid plexus of the MRL/1pr substrain. In addition, the presence of leukocytes correlated positively with measures on one behavioural test (floating in the forced swim test) but not on another test (novel object test). These findings suggest that CY treatment has a differential effect on the infiltration of leukocyte subtypes and strengthen the hypothesis that some abnormal behaviour in MRL/1pr mice may be related to the presence of immunocompetent cells in the brain.