The in vitro and in vivo activity of the 5 injectable cephalosporins, cefazolin, cephaloridine, cephalothin, cephapirin, cephacetrile, and ampicillin was compared. No gram-positive organisms resistant to any of the cephalosporin derivatives were encountered. The MIC of ampicillin for gram-positive organisms was distributed over a wide range. The antibacterial activity of cefazolin, cephaloridine and ampicillin was high against gram-negative organisms. Ampicillin was potently effective especially against P. mirabilis and cefazolin especially against K. pneumoniae. The protecting effect of the 5 cephalosporins on experimental infections in mice was compared. The effect of cefazolin and cephaloridine was more marked than that of the others. These results may be explained by the fact that the other 3 cephalosporins are rapidly metabolized in the living body.