This study evaluated the efficacy of fludarabine, a new adenine nucleoside analogue, in typical and variant forms of hairy cell leukemia (HCL). Two patients with HCL and one patient with a variant form of HCL (HCL-variant) with resistant or progressive disease with prior treatments were studied. Fludarabine (30 mg/m2) was administered intravenously over 30 minutes daily for 5 days every month. Two patients (one with HCL and one with HCL-variant) achieved partial responses; the third patient had a minor response. This is the first report of encouraging activity of fludarabine in typical and variant forms of HCL. Further experience with fludarabine in these disorders is indicated.