Objective: The aim of the study was to investigate whether the analgesic effect of propyphenazone (PROP) was increased when it was administered in combination with caffeine (GAFF).Methods: For assessment of analgesia a model was chosen based on chemo-somatosensory event-related potentials (CSSERP) elicited by stimulation of the nasal mucosa. Twenty healthy volunteers participated in the experiments. The study followed a placebo-controlled, randomised, double-blind, 5-fold cross-over design. Each of the 5 medications (400 mg PROP, 600 mg PROP, 400 mg PROP + 100 mg GAFF, 600 mg PROP + 150 mg GAFF, placebo) was orally administered. Experiments were separated by at least 5 days. In addition to assessment of CSSERP, subjects estimated the intensity of the stimulus. Drug effects unrelated to nociception were monitored, and in addition, the plasma levels of PROP were also analysed.Results: While 400 mg PROP did not significantly reduce the amplitude of CSSERP in comparison to placebo, all other medications produced a significant decrease in amplitudes. For both dosages of PROP, there was a significant amplification of the antinociceptive effect of PROP by GAFF, as indicated by the decrease in CSSERP amplitude. A significant effect of the factor ''drug'' was also found in the spontaneous EEG, indicating an arousal reaction after CAFE No significant differences between plasma levels of PROP were found when applied either alone or in combination with CAFE.Conclusion: The significant increase in the antinociceptive effect of PROP when administered together with caffeine appears to be related either to amplification of PROP's antinociceptive actions by GAFF or an atinociceptive effect of GAFF itself.