The possibility of an in vitro interaction between the bactericidal activity of fresh normal human serum and the antibiotics polymyxin B, ampicillin, and kanamycin was investigated with strains of Escherichia coli. Mixtures of serum and low concentrations of polymyxin B gave consistently greater reductions of viable counts than did either component individually. This applied with both serum sensitive and serum resistant strains. In contrast, ampicillin and kanamycin gave much less clearcut results. When employing serum sensitive organism, both antibiotics acted slightly additively with fresh serum after seven hours, whereas no such effect was demonstrable in experiments involving serum resistant strains of E. coli. Eight of thirteen strains of E. coli and Enterobacter-Klebsiella isolated from blood culture showed some degree of serum sensitivity.