Locoweed intoxication or locoism results when animals continuously graze certain plants of the general Astragalus or Oxytropis. The locoweed toxin, swainsonine, is water soluble and is rapidly absorbed and eliminated. The purpose of this study was to determine the distribution of swainsonine in tissues of sheep eating locoweed and to determine if the tissue swainsonine concentrations change with continued locoweed ingestion. Fifteen cross-breed whethers were divided into 3 groups of 5 each and fed alfalfa pellets (Group 1) or alfalfa pellets with 10% Astragalus lentiginosus for 13 d (Group 2) or for 21 d (Group 3). After the feeding periods, the animals were slaughtered and tissues were collected, frozen and later analyzed for swainsonine using an in vitro, alpha-mannosidase inhibition assay. Significant alpha-mannosidase inhibitory activity (interpreted as ng/ml of swainsonine) was detected in whole blood, skeletal muscle, brain, kidney, liver, thyroid and urine. The swainsonine concentrations in tissues were significantly correlated with daily swainsonine intake (r = 0.58 to 0.96). With the exception of kidney, longer exposure did not result in significant increases in the swainsonine concentrations in blood, muscle, brain, liver or thyroid. Liver had the highest swainsonine concentrations with 3049 +/- 1952 and 3947 +/- 457 ng/ml (mean +/- SD) in Groups 2 and 3 respectively. Swainsonine concentrations varied widely within the groups suggesting individual animal variability in swainsonine absorption, metabolism and excretion. These findings suggest that swainsonine is present in tissues of animals eating locoweed and that in most tissues the amount was directly correlated to the swainsonine dose ingested, but not to the length of exposure.