1. To test the hypothesis that inhibition of cyclic nucleotide phosphodiesterase is the major mechanism of the bronchodilator action of theophylline in reversible airways disease, the effects of therapeutic plasma levels of the drug on human pulmonary phosphodiesterase activity were examined. 2. Therapeutic levels of theophylline inhibited the phosphodiesterase-catalysed hydrolysis of adenosine cyclic 3',5'-monophosphate (cAMP) and guanosine cyclic 3',5'-monophosphate (cGMP), but the percentage inhibition was relatively small. 3. The results, while supporting the assumed contribution of phosphodiesterase inhibition to the overall mechanism of theophylline action, suggest that other presently unknown factors must also be taken into consideration to fully explain the beneficial effects of theophylline in reversible airways disease.