The in vitro activity of cephalexin, cephaloridine, cephalothin, cephapirin, cefoxitin, cephamycin C, cepharadine and cefazolin was determined against 443 isolates of bacteria. At a concentration of 12.5 mug/ml, all of the cephalosporins inhibited more than 60% of the isolates of Klebsiella pneumoniae. At the same concentration, cephalexin, cephaloridine, cephalothin, cephapirin, cephamycin C and cefazolin inhibited more than 90% of isolates of proteus mirabilis. All of the cephalosporins except cephalothin and cephapirin inhibited over 60% of isolates of Escherichia coli at a concentration of 12.5 mug/ml. Cefoxitin was the most active cephalosporin against gram-negative bacilli. There was substantial differences in the activity of cephalosporins against gram-positive cocci. Cephaloridine was the most active cephalosporin against these organisms. There was considerable fluctuation in the proportion of isolates of gram-negative bacilli susceptible to these cephalosporins from year to year, but there was no evidence to suggest that the number of resistant isolates was increasing.