The causal prophylactic, radical curative, and blood schizontocidal activities of 7-chlorolincomycin (U-21251F) and N-demethyl-4′-pentyl-7-chlorolincomycin (U-24729A) were evaluated against infections with the Bastienellii, RO and RO/PM strains of Plasmodium cynomolgi in Macaca mulatta. Sporozoites for causal prophylactic and radical curative evaluations were derived from Anopheles freeborni fed at appropriate intervals on monkeys bearing infections with the above strains. Over a wide range of tolerated doses, U-21251F effected a delay in the prepatent period in causal prophylactic studies and prolongation of relapse intervals when examined for radical cure. In the same range of doses, U-24729A effected greater lengthening of these intervals; with the largest doses, complete causal prophylaxis and radical cures were achieved in a significant fraction of cases. Prolongation of the prepatent period produced by U-24729A resulted from the effects of this agent on developing pre-erythrocytic parasites. Both U-21251F and U-24729A were as effective against challenges with sporozoites of a pyrimethamine-proguanil-resistant strain of P. cynomolgi as against challenges with a wholly drug-susceptible strain. Both compounds exhibited significant blood schizontocidal activity but were slow in clearing parasitemias. Based on these activities, clinical evaluations of the properties of U-24729A have been suggested.