Plasma samples, obtained at slaughter, from sheep (19), cattle (17), and goats (4) with clinical evidence of M. paratuberculosis infection (Johne's disease) were examined for changes in 10 clinical biochemical parameters (total protein, albumin, globulin, calcium, magnesium, phosphorous, creatinine, urea, AST, GGT). Hypocalcaemia and hypoalbumnaemia were a consistent and characteristic finding in all clinical cases compared, at least in the case of sheep and cattle, with animals with no evidence of mycobacterial infection. Goats were obtained from a farm with a history of Johne's disease and were assumed to have been naturally exposed to M. paratuberculosis. However, of 21 animals examined, only 4 had evidence of clinical lesions and/or PCR reactivity. Of the biochemical parameters measured, only total protein was consistently affected, presumably reflecting the observed loss of albumin. Plasma antibody titers were significantly higher and lymphocyte reactivity low in clinically affected sheep and goats (no data available for cattle). In both species, decreases in albumin and calcium were correlated with both immune markers. Possible implications of these observations, especially with respect to Vitamin D immunomodulation, will be discussed.