We examined the relative susceptibilities of Anopheles gambiae Giles of different physiological ages to infection with cultured Plasmodium falciparum (Welch). Cohorts of mosquitoes were divided into three groups; one was fed uninfected blood on day 3 after emergence (i.e., one prior blood meal); another on days 3 and 7 after emergence (i.e., two prior blood meals); and a control group was maintained on sucrose. On days 10 to 12 after emergence, mosquitoes were fed human blood containing P. falciparum gametocytes. Prior blood feeding accelerated digestion of the infective blood meals and subtly altered susceptibility to infection with P. falciparum. When gametocyte cultures were highly fertile, all experimental groups were equally susceptible to infection. However, when gametocyte fertility was low, accelerated digestion had a detrimental effect on the transition of ookinetes to oocysts. Accelerated digestion may raise the threshold density of ookinetes required for the successful conversion of ookinetes to oocysts.