Subclinical intoxication of livestock with Astragalus and Oxytropis species (locoweeds) results in decreased animal feed conversion, reduced weight gains, and reproductive failure. Sensitive diagnostic methods to definitively diagnose and monitor intoxication are needed to minimize these losses and better manage locoweed-infested pastures and rangelands. Sera from cattle grazing locoweed were evaluated for alpha-mannosidase activity, serum biochemical values, electrolytes, and thyroid hormone concentrations. As the cows began to ingest locoweed, the mean serum alpha-mannosidase activities dropped significantly (400.0 microM to 72.5 microM). Changes in other serum chemistry values were less specific; however, individual animals (generally those ingesting more locoweed) had elevated levels of alkaline phosphatase (ALP), aspartate aminotransferase, and lactate dehydrogenase, with decreased serum total protein (5.8 +/- 0.8 g/dl) and albumin (2.3 +/- 0.3 g/dl). Mean serum thyroid concentrations (both T4 and T3) were lower in animals that were ingesting locoweed. The calculated swainsonine dose correlated statistically with serum alpha-mannosidase activity, ALP, albumin, Cl, CO2, and thyroid hormone T3. This correlation suggests that serum alpha-mannosidase activity along with potential changes in ALP, albumin, and thyroid hormone concentrations is a sensitive indicator of locoweed exposure and intoxication. These parameters may also be useful for monitoring intoxication and allowing subclinically affected cattle to be removed from infested areas before irreversible damage occurs.