Previous studies indicated that the level of whole serum complement (C') falls during malaria, and that the fall in C' is linked to schizont rupture and the appearance of humoral antibody. For a more detailed study of the role of C' in malaria, levels of C4 were monitored in rhesus monkeys infected with Plasmodium coatneyi. After 1 to 2 wk of infection, significant and abrupt declines in C4 levels occurred, and these were temporally related to the process of schizont rupture. The level of C4 began to fall within a few hours after the onset of schizont rupture and fell to values as low as 2% of prerupture levels. Over the next 24 to 36 hr, C4 returned to normal levels, and fell again during the next cycle of schizont rupture. In general, the decline in C4 levels was positively correlated with the onset of immune response (functional and serologic) and degree of parasitemia. This marked cyclical depletion of C4 indicates tremendous turnover of C' in primates with malaria.