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Several milk components related to immune defences (lysozyme, lactoferrin and γ-globulins, γ-G) and to inflammation (somatic cell counts, SCC; N-acetyl-β-glucosaminidase, NAGase; albumin) were considered. Forty-one quarters and 685 samples of 24 cows were included in the study; among them 534 samples were defined as negative (78·0%), 93 as diseased (13·5%) and 58 (8·5%) as subclinical. The pattern of each milk component in quarters always negative during the follow-up period was evaluated by a mixed model. Statistical analysis showed that days in milk (DIM), age (primiparous, pluriparous), herd and the interaction between herd and days in milk significantly influenced all the markers, with very few exceptions. A subset of samples including the negative quarters before the first outcome of an infection or a subclinical mastitis and the samples from quarters always negative was also selected. The analysis showed that herd, DIM and health status had a significant influence on most markers. Overall, primiparous cows were confirmed to have higher levels of most of the markers than pluriparous cows. The presence of a herd effect on non specific immune defences in fully negative quarters implies that when the mechanisms behind their release are fully elucidated, it might be possible to modulate them. Udder tissues were confirmed as an important source of some immune components, as supported by the inconsistency between SCC mean values and NAGase, lysozyme and lactoferrin values. Overall, quarters with high levels of NAGase, lysozyme and γ-G, exposed to bacteria, did not develop subclinical mastitis. Hence, invading pathogens could induce the development of subclinical IMI when these components and γG are in low concentration. [ABSTRACT FROM AUTHOR]