Objectives were to: (1) find systemic compounds which, when given orally to rats, kill oriental rat fleas, Xenopsylla cheopis (Rothschild); (2) determine the lowest dosage level to produce a significant mortality of fleas; and (3) determine the duration of systemic effectiveness. Nine of the 21 compounds evaluated produced more than 50% mortality of fleas. Five were subjected to more extensive studies: dimethoate, Bayer 29493 ( O, O -dimethyl O -[4(methylthio)-m-tolyl]phosphorothioate), American Cyanamid CL 38064 (phosphorothioic acid, O-p -(ethylsulfamoyl) phenyl O, O -dimethyl ester), American Cyanamid CI 38023 (phosphorothioic acid, O, O -dimethyl O-p -(dimethylsulfamoyl)-phenol ester), and Dylox® ( O, O -dimethyl-2,2,2-trichloro-1-hydroxyethyl phosphonate). Each of the 5 compounds, except Dylox, was used in two experiments. The first consisted of confining fleas on dosed rats: (1) one hour after dosing and permitting them to feed for 3 hours; (2) four hours after dosing and permitting them to feed for 8 hours; and (3) twelve hours after dosing and permitting them to feed for 12 hours. The second experiment consisted of confining fleas on dosed rats for a 3-hour feeding period after delays between dosages and opportunity for initial feeding of 1, 4, 7 and 10 hours; mortality at 13 hours after dosing was determined following a feeding period of 11 hours. Dimethoate at 50 mg./kg. produced a high mortality of fleas following a 1-hour delay between dosing and feeding but all effectiveness had dissipated by 4 hours following dosing. Bayer 29493 produced a high mortality of fleas at 75-150 mg./kg. after a 1-hour delayed feeding period and retained relative effectiveness for a period exceeded only by CL 38064 and about equal to CL 38023.