Clinical ostertagiosis occurs under three sets of circumstances called type I, pre-type II, and type II diseases. The type I disease is seen in calves at pasture, shortly after a period of high availability of infective larvae. It is due to the direct development of large numbers of L3 larvae to adult worms over a relatively short period of time. In contrast, type II disease is due to the synchronous maturation and emergence of large numbers of hypobiotic larvae from the mucosa and occurs when intake of larvae is likely to be low or nonexistent. It occurs in cattle, mainly yearlings or heifers, during the winter in the northern hemisphere or during the dry summer period in Mediterranean climates. The almost asymptomatic condition which precedes type II ostertagiosis has been called pre-type II. In this phase, the abomasum carries a pathogenically adequate burden of inhibited larvae which are still quiescent, but from which disease type II may erupt unpredictably if a sufficiently large number of larvae resume development to maturity. In sheep the same forms occur, but in ewes the course of type II is very rare and more chronic. Clinical signs start at the time the parasites reach maturity; they begin to emerge from the gastric glands (in type I after 18–21 days and in type II after 4–6 months) and marked cellular changes appear. The functional gastric gland mass, particularly the hydrochloric acid (HCl)-producing parietal cells, is replaced by undifferentiated cells. It has also been shown that the secretory activity of parietal cells is blocked. The undifferentiated and hyperplastic mucosa is abnormally permeable to macromolecules following the destruction of the intercellular junctions. This happens not only in the parasitized gastric gland but also in the surrounding glands. These structural changes result in: (1) an elevation of the pH of the abomasal fluid from 2 to 5 or even higher. This leads to a failure to activate pepsinogen to pepsin and to denature proteins. There is also a loss of bacteriostatic activity, which is followed by an increase in the number of bacteria; (2) an enhanced permeability to macromolecules resulting in hypoalbuminemia, the albumin in the plasma passing into the abomasum. Any loss of protein macromolecules is usually accompanied by loss of electrolytes, mainly Na+ and Cl−. The onset of diarrhea increases the loss of electrolytes. Continued loss may lead to increased hypoalbuminemia, retention of fluid, and the development of oedema; (3) elevated plasma pepsinogen concentrations of more than three U tyrosine. The mechanism responsible for this increase is not yet completely understood. A multifactorial cause has been postulated, involving direct stimulation of zymogenic cells by factors released from the parasite, indirect stimulation via elevated circulating concentrations of hormones such as gastrin (vide infra), and leakage from abomasal fluid between poorly differentiated epithelial cells; (4) raised gastrin levels. The gastrin levels have been found to increase considerably during Ostertagia infection in sheep and cattle. The consequences are not clear. Gastrin has a multiplicity of actions, e.g., stimulating HCl and pepsinogen secretion, inhibiting reticulo-ruminal motility, and trophic effects on the gastric and intestinal mucosa. The cause of hypergastrinemia has not been established but the presence of the parasite seems to be critical.