The rectal absorption of aspirin from theobroma oil suppositories was studied in seven human subjects using urinary excretion measurements. The effect of particle size on the excretion rate and cumulative amount of total salicylate excreted was demonstrated by the administration of a 600-mg dose as powdered aspirin and as aspirin disks having 0.023 as much surface as powdered aspirin. In vitro dissolution profiles of aspirin from the suppositories were studied. By the NF XIII Method II, the time required for 50% of the aspirin to dissolve from the suppository was 50 and 100 min for the powdered aspirin and the aspirin disks, respectively. In the bioavailability study, the diffusion equilibrium was attained at approximately 4-5 and 9-10 hr after the rectal administration of powdered aspirin and aspirin disks, respectively. No correlation was found between bioavailability and the dissolution profiles as determined by the USP XVIII dissolution method.