Malaria remains one of the most important disease of human in terms of both mortality and morbidity, with Plasmodium falciparum being the most important species. The emergence and widespread of chloroquine resistance of falciparum parasites is one of main reasons for failure of global malaria eradication program and resurgence of the malaria in recent years. Development of malaria vaccine has proved to be more difficult than expected, due to antigenic variation of the parasites and genetic restriction of their host. Nowadays, many of researchers on malaria have concentrated on exploring new avenues to the control of the disease rather than the parasites. Chloroquine-sensitive strain (N) of Plasmodium berghei is lathal and Chloroquine-resistant strain (RC) of P berghei nonlathal, and the latter derived from the former by selection of chloroquine in vivo. The present studies investigated difference of virulence between the N strain and the RC strain and explored the mechanism which is responsible for the difference. 1. Difference of virulence: l).Relation of parasitaemia with temperature and body weigh of the mice: Some of mice infected with the N strain by peritoneal injection of ix 106 parasitized erythrocytes/per mouse appeared dead on postinfection 9~ day. No survivals remained among the mice with the N strain on postinfection list day and mortality 100%. Body weigh of the mice with the N strain tended to increase before postinfection &?day then to decrease gradually. Temperature of the mice with the N strain remained about 370C before postinfection 7~ day and dropped by degrees until all of them died. Some of mice infected with RC strain appeared dead on postinfection 24~ day with mortality of 25%. The parasites disappeared from the most of them on postinfection 36th day. Weigh of the mice with the RC strain tended to increase and their 6 temperature remained about 36.50C in the first 16 days of the infection and decreased gradually after that time. The body weigh of them decreased to 92.60%+ 4.59% and their temperature dropped to 29.90 0C+ 0.58 0C in postinfection 26~~?to 28di days. Their body weigh returned to 105.00%+5.80% and their temperature to 36.700C+0.24 0C on the 36~ day. 2). Difference in the number of erythrocytes, spleen weight and liver weight: The number of erythrocytes, spleen weight and liver weight of the mice infected with the N strain or the RC strain were 2.45x106/mm3+1.19x106/mm3, l.71%?.51%, 7.20% 6 +0.49% and 2.OlxlO /mm3+0.79x106/mm3 4 08%+1.12%, 8.68%+1.18% respectively, when the parasitaemia of the mice infected with N strain or RC strain was at 64.82% ?.65% and 63.35%?.66%. The number of erythrocytes in both of the mice with the N strain or the RC strain was much significantly smaller than that of the control mice. The spleen weigh and the liver weigh in both of them were heavier than that of the control mice also (p<0.0 1). Spleen weight and liver weight of the mice infected with RC strain were significantly heavier than those of the mice infected with N strain. 3). Histopathologic changes: Heavy hemozoin deposited in liver and spleen of mice infected with the N strain, and the lungs appeared stagnant edema. Congestion and embolism were formed, which comprised leucocytes and erythrocytes infected with