For assessment of the underlying central mechanisms of interferon (IFN), measurements have been made of the neurotoxicity, cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) concentrations, along with electroencephalographic (EEG) recordings and visual evoked potentials (VEP) during recombinant IFN-gamma therapy. Interferon-gamma was administered intravenously to 14 patients with non-small-cell lung cancer as 2 mg/m2 (48 X 10(6) IU/m2) three times weekly with 4 h infusion for 12 weeks. The cerebrospinal fluid (CSF) samples were taken by means of lumbar puncture prior to treatment and during the end of the second week of IFN-gamma infusions. During the course of treatment, CSF 5-HIAA diminished from 129.6 +/- 10.9 to 84.5 +/- 10.4 nmol/L (p less than 0.001), while no significant changes were observed in HVA, EEG, and VEPs. These results suggest that IFN-gamma has an effect on the central serotonergic neurotransmission.