Immunosuppressive regimens for lung transplantation frequently fail to prevent rejection and are toxic. Alemtuzumab was used as induction to investigate whether oral immunosuppression could be reduced. From November 2006 to March 2008, 20 consecutive lung transplant patients received alemtuzumab induction, with reduced maintenance immunosuppression; tacrolimus (target level 10 ng/ml), mycophenolate mofetil (MMF) 250 mg bid and prednisone 7.5 mg. Twenty control cases transplanted before 2006 were treated with standard immunosuppression; tacrolimus (target level 10 ng/ml), MMF 750 mg bid and prednisone 15 mg qd. End-points included patient and graft survival, acute rejection (AR) and infection rate. There were no significant differences in six-month and 12-month survival (alemtuzumab 90% vs. controls 95%, P=0.52 and 76% vs. 95%, respectively, P=0.19). AR events were similar (alemtuzumab 2/16 vs. controls 5/20, P=0.43) - as were - bacteria positive bronchoalveolar lavage (BAL) cultures (alemtuzumab 4.9+/-7.3 per patient per year vs. controls 2.7+/-3.3, P=0.26) and viral or fungal infections (alemtuzumab 0.4+/-1.4 per patient per year vs. controls 0.1+/-0.3, P=0.87; alemtuzumab 3.9+/-6.6 vs. controls 2.3+/-1.9, P=0.57, respectively). Alemtuzumab induction and reduced immunosuppression appears to offer comparable early survival, rejection and infection rates to high-dose standard immunosuppression.