Cefazblin was tested in vitro for its reactivity in the direct Coombs test as compared to other related antibiotics. Minimal concentrations of the antibiotics which were required to produce a direct Coombs reaction were 2.5 mg/ ml for cephalothin, 5 mg/ml for benzyl penicillin, 10 mg/ml for cephaloridine, and 40 mg/ml for cefazolin. Cefazolin even at this high concentration gave only a weak positive reaction and this depended upon the Coombs serum employed. The intensity of the positive reaction was apparently related to that of the direct antibiotic-induced lytic action on the red blood cells used (cephalothin >benzyl penicillin >cephaloridine> cefazolin). These positive reactions are believed to arise from the binding of normal globulin, directly, or otherwise indirectly through antibiotics, to the surface of red blood cell walls which have been impaired by the antibiotics. It seems therefore that these phneomena in vitro are not immunological in nature.