Abstract This report summarizes the results of a comparative study of the major features of untreated infections with the B strain of Plasmodium cynomolgi in Macaca mulatta, M. irus (fascicularis), M. nemestrina, M. speciosa (arctoides), and Cercopithecus aethiops. The investigation included: delineation of the courses of trophozoite-induced and sporozoite-induced infections in these Old World primates; evaluation of their efficiencies in transmitting the above plasmodium through Anopheles freeborni; and assessment of host reactions to infection, with particular attention to impacts on erythroid elements of peripheral blood. In all important respects, the parasitic courses of infections in M. mulatta and C. aethiops (Kenyan origin) were identical, as were the reactions of these hosts to disease processes. M. mulatta was slightly more efficient than C. aethiops in transmitting P. cynomolgi through A. freeborni; however, this favored position may have been purchased by experimental design. The features of infections in M. irus, M. nemestrina, and M. speciosa differed significantly from those in M. mulatta. M. irus responded to challenge with trophozoites or sporozoites in a highly reproducible manner, but exhibited peak parasitemias and a long series of parasitic waves (recrudescences and/or relapses) of much lower intensities than were encountered in M. mulatta. M. nemestrina responded to such challenges in diverse manners. A few subjects exhibited parasitic courses almost identical with those encountered in M. irus. The majority exhibited extremely low level parasitemias of great persistence. These diverse parasitic courses were associated with specific physical features of this monkey. M. speciosa failed to support infections following inoculation with either trophozoites or sporozoites. Sporozoite challenges did lead to transient, extremely low level parasitemias, indicating that tissue stage schizogony had taken place. The unusual features of infections in M. nemestrina and M. speciosa could be of substantial interest to those concerned with factors which determine invasion of erythrocytes by plasmodia. Demonstration that untreated infections in M. mulatta and C. aethiops are essentially identical is of far more immediate importance. If responses of infections in these hosts to standard antimalarial drugs are also identical, the way is open to substituting C. aethiops for M. mulatta in studies on the biology and therapy of infections with P. cynomolgi, particularly in the search for radical curative drugs. Such substitution would meet a critical need at a time when access to feral M. mulatta is restricted.