Blood neutrophil functions, lymphocyte blastogenic responses, serum complement, and serum conglutinin activity of 98 lactating Holstein cows from two genetic lines were evaluated. The genetic lines were produced in a selection experiment that created and perpetuated genetic differences in milk production for up to seven generations. No significant differences between the two genetic lines of cows were found for neutrophil function, lymphocyte blastogenic responses, serum complement levels, or serum conglutinin levels. Significant differences between sire progeny groups within lines were found for unstimulated and mitogen-stimulated lymphocyte blastogenesis ( P<0.0001), and almost all neutrophil functions (antibody independent neutrophil cytotoxicity, antibody dependent neutrophil cytotoxicity, ingestion of bacteria, iodination, chemiluminescence, chemokinesis, and chemotaxis ( P≤0.05)). Sire progeny group differences ( P≤0.0001) within lines for serum complement and conglutinin activity were also found. Neutrophil chemiluminescence activity (positive relationship; P≤0.001), concanavalin A-stimulated lymphocyte blastogenesis (positivee relationship; P≤0.004), and serum conglutinin activity levels (negative relationship; P≤0.01) each had small but significant associations with the total milk somatic cell count. Cows seropositive for bovine leukosis virus had increased resting and mitogen-stimulated lymphocyte blastogenic activity and were associated with increased in vitro neutrophil random migration and production of superoxide anion. Estimates of genetic parameters of various immune cell functions, of serum complement and of conglutinin levels for daughters of 11 sires with 4–6 daughters in the data set were determined. In this report, genetic variation was demonstrated for nonspecific humoral and cellular immunity.