1. The free and total plasma and saliva concentrations of theophylline were measured during a dosing interval at steady state in nineteen asthmatic subjects receiving a once-daily theophylline preparation (Riker TCR-1). 2. Saliva theophylline clearance (mean +/- s.d. 5.8 +/- 2.1l h-1) was closely related to total plasma theophylline clearance (mean 3.6 +/- 1.2l h-1) (r = 0.958, n = 19, P less than 0.001). 3. Saliva theophylline clearance was closely related (r = 0.967, n = 19, P less than 0.001) and numerically very similar to the free plasma theophylline clearance (mean 5.8 +/- 1.9l h-1) (mean difference = 0.06 +/- 0.12 s.e. mean). 4. Free plasma theophylline clearance was significantly, although weakly, related to body weight and to the plasma free thyroxine concentration which together accounted for over 40 per cent of the variability in free clearance. 5. Theophylline administered for 2 weeks did not affect plasma free thyroxine (FT4) free tri-iodothyronine (FT3) or reverse tri-iodothyronine (rT3) concentrations compared with placebo.