The ookinete is one of the most important stages of Plasmodium develop
ment in the mosquito. It is morphologically and biochemically distinct
from the earlier sexual stages - gametocytes and zygote, and from the
later stages - oocyst and sporozoites. Development to ookinete allows
the parasite to escape from the tightly packed blood bolus, to cross
the sturdy peritrophic matrix (PM), to be protected from the digestive
environment of the midgut lumen, and to invade the gut epithelium. Th
e success of each of these activities may depend on the degree of the
biochemical and physical barriers in the mosquito (such as density of
blood bolus, thickness of peritrophic matrix, proteolytic activities i
n the gut lumen etc.) and the ability of the ookinete to overcome thes
e barriers. Ookinete motility, secretion of chitinase, resistance to t
he digestive enzymes, and recognition/invasion of the midgut epitheliu
m all may play crucial roles in the transformation to oocyst. The over
all sporogonic development of Plasmodium, therefore, depends on the re
sults of the two-way manipulations between the parasite and the vector
mosquito. Study of ookinete development and of the cellular and bioch
emical complexities of the mosquito gut may therefore lead to the desi
gn of novel strategies to block the transmission of malaria. This arti
cle reviews the intricate interactions between the parasite and the mo
squito midgut in the context of development and transmission of Plasmo
dium parasites.