The objective of monitoring theophylline plasma levels in therapeutic work is well established, and the consequences of using unspecific analytical methods are obvious. For the determination of pharmacokinetic parameters, concentrations far below the therapeutic range must often be measured. Interferences acceptable in therapeutic monitoring of theophylline could cause severe inaccuracy at these drug levels. The term specificity and its meaning are discussed in general and in relation to the different steps of the analytical procedure (e.g., sampling and sample work-up). Different analytical methods for theophylline are discussed in terms of specificity. Plasma concentrations of paraxanthine (1,7-dimethylxanthine)--a metabolite of caffeine--as high as 3 microgram/ml have been observed, and the compound can interfere in various theophylline assay methods. An example is given of the pharmacokinetic consequences.