To simplify the L-[1-13C]phenylalanine breath test which is used to assess liver function the tracer is usually given orally, and CO2 production rate is estimated. In 12 healthy volunteers and 10 liver cirrhotics we compared the oral approach with i.v. tracer administration combined with measurement of individual CO2 production rate. The 13CO2/12CO2 enrichment was assessed by isotope-ratio mass spectrometry. After i.v. [1-13C]phenylalanine application exhaled 13C recovery per minute peaked within 10 minutes (controls: 0.17 +/- 0.06%; cirrhotics: 0.05 +/- 0.02%, p < 0.01). The oral approach yielded comparable separation between 30-60 minutes, with average peak values being 0.18 +/- 0.03% and 0.06 +/- 0.03% (p < 0.01), respectively. Variable gastrointestinal resorption kinetics after oral application probably causes this difference.