The pharmacokinetics and bioavailability of theophylline from a commercial oral elixir of theophylline, a rectal suppository of aminophylline, and a rectal enema of theophylline monoethanolamine was compared in six normal subjects. Using a complete crossover design, the fasted subjects received a single dose of each dosage form. Blood and saliva samples were collected at frequent time intervals for 24 h, and the plasma assayed for theophylline by a specific thin-layer chromatography densitometric method. No statistically significant differences existed among the three dosage forms with respect to Cmax and AUC corrected for the elimination rate constant and the dose (mg kg-1). However, tmax was significantly larger for the suppository. While the rate of absorption was significantly slower for the suppository, no differences in the extent of absorption existed among the three dosage forms. A one-compartment open model with apparent first-order absorption adequately described the plasma concentration-time data for the elixir and enema, whereas the suppository data were best fitted by a one-compartment open model with apparent zero-order absorption and a lag time. A rate-limiting, concentration-independent release of drug from the base most likely accounts for the slow absorption of theophylline from the suppository. While the saliva:plasma ratio remained fairly constant for most of the study period, the large variability found during the absorption phase following drug administration limits the usefulness of this parameter as a monitor of theophylline plasma concentrations.