Possible immunomodulation by low-level infection with Ostertagia ostertagi was studied in 4-month-old calves. Six groups of 4 calves each were subjected to the following regimes: group 1--nonparasitized controls; group 2--nonparasitized, but challenge exposed at day 64 with Brucella abortus strain 19 vaccine (BA) and at day 78 with IV administration of a soluble third-stage larval (L3) antigen preparation of O. ostertagi (OAG); group 3--nonparasitized, but challenge exposed at day 78 with 75 X 10(3) L3 of O ostertagi; group 4--continuously parasitized by weekly dosing with 30 X 10(3) L3 of O ostertagi; group 5--continuously parasitized by weekly dosing with 30 X 10(3) L3 of O ostertagi, then challenge exposed on day 64 with BA and on day 78 with IV inoculation of OAG; and group 6--continuously parasitized by weekly dosing with 30 X 10(3) L3 of O ostertagi, then challenge exposed on day 78 with 75 X 10(3) L3 of O ostertagi. Over the initial 10 weeks of the study, nonparasitized calves, (groups 1, 2, and 3) had higher body weight, blood lymphocyte (BL) response to phytohemagglutinin (PHA), and significantly (P less than 0.05) higher feed consumption and lymphocyte numbers, whereas parasitized calves (groups 4, 5, and 6) had higher BL responses to pokeweed mitogen (PWM) and significantly (P less than 0.05) higher neutrophil and eosinophil numbers, plasma pepsinogen (PP) values, and BL response to OAG. During the challenge-exposure period (weeks 10 through 13), group-5 calves had significantly (P less than 0.05) higher eosinophil numbers and PP values for week 11 (BA challenge exposure) and for week 13 (OAG challenge exposure) than did group-2 calves, but differences were not observed in BL responses to PHA, PWM, and OAG. Oral L3 challenge exposure at week 13 induced significantly (P less than 0.05) lower lymphocyte numbers, higher eosinophil numbers (P less than 0.05), and higher PP values, but lower BL response to PHA, PWM, and OAG in group-6, compared with group-3 calves. In continuously parasitized calves, comparison of IV OAG challenge exposure with oral L3 challenge exposure indicated that group-6 (L3) calves has significantly lower (P less than 0.05) lymphocyte numbers and higher PP values than did group-5 (OAG) calves. Results of ELISA revealed significantly (P less than 0.05) higher antibody titer to OAG in parasitized calves, compared with nonparasitized calves. Abomasal mucosal pathologic changes were most severe in the continuously parasitized calves. Calves of groups 4, 5, and 6 had thicker mucosae (edema), significantly (P less than 0.05) higher eosinophil numbers, and higher globule leukocyte and mast cell numbers in the fundic and pyloric regions than did calves of groups 1, 2, and 3. Calves of groups 4, 5, and 6 also had significantly (P less than 0.05) larger abomasal lymph node masses than did nonparasitized calves. In group-1 calves, nodes had the lowest mass. Differences were not observed among groups for lymphocyte responses to proliferative and suppressive assays performed on the abomasal lymph node lymphocytes.