The quantification of liver function is possible using the approach of salivary caffeine clearance. Hepatopathy sometimes complicates cystic fibrosis (CF), thus suggesting the use of this diagnostic tool in CF as well. Since in CF some compounds are poorly absorbed or abnormally metabolized, and the function of salivary glands or renal tubuli partly impaired, caffeine was measured in urine, blood, and saliva after a single oral dose of 3 mg/kg in CF patients. The urinary excretion rate of caffeine was normal in five CF patients. The caffeine levels in plasma or saliva, measured 4 to 5 h and 16 to 17 h after caffeine intake, were normal in 34 nonhepatopatic CF patients. The calculated salivary caffeine clearance was comparable in the 34 nonhepatopatic CF patients (1.88 +/- 0.46 ml/min/kg) and in the control group (1.88 +/- 0.44 ml/min/kg). In CF patients, no correlation was found between caffeine clearance and body weight, height, relative underweight, dosage of pancreatic enzymes, or Chrispin-Norman x-ray score. The salivary caffeine clearance was reduced in seven hepatopathic CF patients (1.32 +/- 0.63 ml/min/kg, p less than 0.01); nevertheless, the salivary caffeine clearance was reduced (boundary line at 1.1 ml/min/kg) in three CF patients with proven liver cirrhosis but not in four with hepatosplenomegaly and altered liver tests. These data indicate an unaltered caffeine metabolism in CF and open the way for the use of this diagnostic procedure in CF as well. This test might be valuable in CF patients with clinical or laboratory findings suggesting liver involvement.