The bioavailability of allopurinol from orally administered tablets and rectally administered suppositories is reported. Two types of rectal suppositories (cocoa butter and polyethylene glycol) were compounded and contained 300 mg allopurinol (from oral tablets). Five healthy volunteers received 300 mg allopurinol orally from tablets or rectally from suppositories in a randomized, three-way crossover design. Serial blood samples were drawn for 72 hours following administration and were analyzed by high-pressure liquid chromatography for allopurinol and its metabolite, oxipurinol. The interaction between allopurinol and PEG was studied in vitro using a dialysis method. Serum allopurinol levels following oral administration of tablets peaked at 1.5 +/- 0.23 microgram/ml at 5.20 +/- 0.65 hours. Allopurinol was not detectable after administration of cocoa butter/allopurinol suppositories; oxipurinol peaked at 0.34 +/- 0.14 microgram/ml at 13 +/- 11 hours. The bioavailability of allopurinol from the cocoa butter suppository, relative to the tablet, was 5.77 +/- 2.5%. Neither allopurinol nor oxipurinol was detectable (less than 0.1 microgram/ml) in the sera of persons following administration of PEG suppositories. Dialysis studies showed decreased loss of allopurinol from the dialysis sac as PEG concentration increased. The rectal suppositories of allopurinol used in this study did not appear to be an efficient means of administering this drug.