The pharmacokinetics, organ distribution, metabolism and excretion of glucosamine were studied in the dog giving uniformly labelled [¹⁴C]-glucosamine (sulfate), i.v. or orally, in single doses.  Immediately after i.v. administration, the radioactivity in plasma is due to glucosamine, and freely diffuses into organs and tissues.  This radioactivity disappears quickly from plasma (initial t_1/2 = 118 min).  After 30-60 min the radioactivity in plasma is no longer due to glucosamine, but is incorporated into a- and b-globulins.  The protein-incorporated radioactivity is found already 20-30 min after i.v. administration, reaches a peak after 8 h and then slowly disappears, with a t_1/2=2.9 days.  Of the administered radioactivity, more than 34% is excreted in the urine, mainly as glucosamine, and 1.7% is excreted in the feces.  Radioactivity is excreted also as [¹⁴C]-CO2 in the expired air.  The radioactivity, after i.v. administration, diffuses rapidly from blood into the body.  Some organs show an active uptake of radioactivity, e.g. the liver and the kidney.  Other tissues, such as the articular cartilage, also have an active uptake.  In most other organs the radioactivity found can be explained by passive diffusion processes from plasma.  After oral administration of a single dose of [¹⁴C]-glucosamine the radioactivity is quickly and almost completely absorbed from the gastrointestinal tract.  The pattern of disappearance, meta-bolic transformation, tissue distribution and excretion of the radioactivity are consistent with those found after i.v. administration. In man unlabelled glucosamine sulfate (Dona  200-S) was given i.v. and orally and glucosamine was measured in plasma and urine with a glucosamine-specific ion-exchange chromatographic method.  The results show that the bioavailability, pharmacokinetics and excretion pattern of glucosamine are consistent with those found in the dog with radiolabelled glucosamine, and with those reported in a previous study in the rat.  Glucosamine is a small molecule (m.w. = 179.17), very soluble in water and soluble in hydrophilic organic solvents such as methanol.  At 37°C glucosamine has a pK_a of 6.91.  This means that at pH 7.4, e.g. in the blood, 25% of glucosamine is ionized, and 75% is not ionized.  At pH 6.8, e.g. in the small intestine, 46% is ionized and 54% is not ionized.  At pH 1-3, e.g. in the stomach, glucosamine is completely ionized.  The pK_a of glucosamine is therefore very favorable for an absorption from the small intestine and, in general for the crossing of biological barriers in the body.  All these properties candidate glucosamine as an easily absorbable and easily diffusible substance, as in fact it was experimentally found.  After i.v. administration to the dog, glucosamine is found in plasma in a "free" form.  In this form it is not protein-bound, is freely diffusible through biological membranes, and is selectively concentrated in some organs, first of all in the liver and in the kidney, but also in other tissues, e.g. in the articular cartilage.....After oral administration to the dog, glucosamine is rapidly and largely absorbed from the gastrointestinal tract.  Its pharmacokinetics, distribution, metabolism and excretion pattern are consistent with that found after i.v. administration....the results show that the pharmacokinetics of glucosamine in man after i.v., or oral administration does not differ substantially from that found wth radioactive glucosamine in dogs and rats.