Theophylline concentrations were determined by fluorescence polarization immunoassay (FPIA) in saliva, serum and serum water of healthy volunteers and outpatients after administration of single , theophylline doses, and after the administration of several doses in order to establish a steady state. The ! FPIA allowed rapid and reliable theophylline determinations in saliva and serum water (between-days j coefficients of Variation: < 3%; recovery: 95 -103%). Salivary theophylline concentrations measured by l, ' FPIA in 30 samples agreed well with those determined by HPLC. Furthermore the results obtained by j ultrafiltration for the concentration of unbound theophylline in serum water were in good agreement with those determined by ultracentrifugation. The binding of theophylline by serum protein rose by about 25%, when the pH of the samples was increased from 7.0 to 8.0. After adjusting the pH to 7.4, average values for l theophylline binding to proteins at 25 °C ranged from 48.5 to 52.2% in serum samples from outpatients and healthy adults. Salivary theophylline concentrations correlated well with total and free serum theophylline concentrations in healthy adults and outpatients (r = 0.90-0.98). The theophylline concentration in saliva was on average about 20-30% higher than the unbound theophylline concentration in serum water. The l saliva/serum concentration ratio of theophylline showed some intersubject Variation (0.68 ± 0.08; ränge: 0.50-0.85). Using the inean saliva/serum concentration ratio of the patient group, steady state serum .theophylline concentrations were predicted from salivary levels with a mean error of 7.6% (ränge: 0.0-26.8%). The salivary theophylline concentration appears to be a suitable parameter for assessment of compliance, for identification of patients with inappropriate dosage, and for consequent dosage adjustment.