The multiplicity of sustained-release preparations of theophylline. the variety of formulations used and the efficacy claims for the products led to the need for a comparative bioavailability study. Direct in vivo methods were applied to 4 products and a standard preparation. The extent of bioavailability of the 4 products examined, measured relative to a standard solution of theophylline, varied from (mean ± S.D.): 78% ± 40% to 123% ± 23%. Cumulative absorption profiles determined using the Wagner-Nelson method also showed large differences among products. The results are discussed with reference to formulation of the products. Older methods of controlling the release of drugs from solid oral forms performed relatively poorly compared with modern systems.