Four groups of three lambs were used to investigate the pathophysiological changes during the development of a protective immunity against Ostertagia leptospicularis induced by a trickle infection. Three groups (A, B and C) were infected daily with 1000 third-stage larvae (L3) for a period of 26 weeks; group D remained uninfected until challenged. Egg excretion ceased after about 10 weeks in groups A, B and C and at the end of the trickle infection no parasites were found in group A sheep after slaughter. The sheep of groups B and C were highly refractory to two challenge infections, with 100,000 and 200,000 L3, given four and 17 weeks after the end of the trickle infection. Both challenge infections were followed by short term increases in the concentrations of gastrin and pepsinogen in the serum. Group C sheep were immunosuppressed with flumethasone during the second larval challenge and had higher pepsinogen concentrations but similar gastrin concentrations to the untreated sheep of group B.