Cephalothin and cephaloridine are absorbed poorly from the gastrointestinal tract and are effective only by the parenteral route. Cephaloglycin is absorbed better when given orally but not as well as cephalexin. Comparison was made in this study of the effect of the four drugs in the therapy of rhesus monkeys infected, intravenously, with a Group A hemolytic streptococcus at a dose level lethal to untreated controls. With this model, cephaloridine prevented death in monkeys receiving only 12.5 mg/kg/day. Cephalexin given intragastrically was as effective as cephalothin given intramuscularly at dose levels of 25 or 50 mg/kg/day. After the former dose two of four survived in each group, while after 50 mg/kg seven of eight and six of eight receiving cephalothin and cephalexin, respectively, survived. Higher doses of cephaloglycin were required and three of four survived after 100 mg/kg doses. The availability of an effective orally-absorbed cephalosporin would be desirable. These data suggest that cephalexin, in particular, shows promise in this area.