The aim of this study was to determine whether active systemic lupus erythematosus (SLE) is associated with recruitment of resting CD45RA+ T cells or reactivation of CD45RO+ memory T cells. Three-colour immunofluorescence was used to determine CD45 isoform expression by CD4+ T cells from 28 patients with SLE. Newly recruited and highly differentiated primed T cells were distinguished by their CD45RB expression. The pattern of CD45 isoform expression varied directly with time since the onset of symptoms in patients with active SLE. Shortly after symptoms appeared, most cells were CD45RA+ resting cells or CD45RO(dull)RB(bright) early primed cells. However, over the course of active disease, patients accumulated CD45RO(bright)RB(dull) cells which represent an advanced state of differentiation. The switch from an early to late primed phenotype correlated significantly with time since the onset of symptoms. The recruitment of resting T cells in active SLE, rather than the simple reactivation of existing memory clones, has implications for understanding the pathology of this disease and for treating it.