Allopurinol exhibits good bioavailability (78-90%) after administration of oral dosage forms to humans and rabbits; however, it is not absorbed rectally from any of the dosage forms to any significant extent. Oral administration of allopurinol in a polyethylene glycol suspension, to which allopurinol may be reversibly complexed, to rabbits has been shown to produce erratic and poor absorption of allopurinol. This suggests the possibility of differential absorption of allopurinol from various sites of the GI tract. The mechanism of allopurinol absorption was investigated in rats using the in situ Levine technique. The allopurinol absorption rate was 0.56 +/- 0.10 microgram/min/cm from the upper portion of the small intestine and was 0.48 +/- 0.12 microgram/min/cm from the midgut. The absorption from the lower portion of the small intestine was 0.33 +/- 0.14 microgram/min/cm and from the upper and lower large intestine segments was negligible (0.04 +/- 0.06 microgram/min/cm). The normalization of these absorption rates for surface area yielded flux values (normalized absorption rate as microgram/min/cm2) with significant differences in permeability between small and large intestine for allopurinol. The allopurinol absorption rate increased with increases in the dose, and there was a linear relationship between dose and absorption rate. Thus, allopurinol absorption, although specific to particular sites, is not dose dependent in the dose range from 0.25 to 2.5 mg/mL. Differences in the rates of absorption may be due to anatomical differences of the various parts of the GI tract or due to physicochemical properties of the drug itself.