Cefamandole nafate and cephalothin sodium were administered as prophylaxis in a randomized, prospective study to 80 consecutive patients undergoing open heart surgery. The two groups matched well in age, sex, and type of operation. Postoperative infection developed in 2 of 40 patients (5%) in the cefamandole-treated group and in 11 of 40 patients (27.5%) in the cephalothin-treated group (p less than 0.01). The two patients in the former group had respiratory tract infections. There were no instance of endocarditis, mediastinitis or bacteraemia in any of the two groups. Both antibiotics were well tolerated with no adverse reactions. Cefamandole appears to be an effective and preferable prophylactic antibiotic for use during cardiac surgery.