Nalbuphine is a mixed opioid agonist/antagonist, the analgesic properties of which are still open to debate. In a randomized and placebo-controlled protocol, we compared its effects (0.2 mg/kg) on man's perception of multimodal stimuli (i.e., nociceptive, acoustic and visual) to those of aspirin (acetylsalicylic acid, 10 mg/kg) and meperidine (0.5 mg/kg). Amplitudes and latencies of the evoked potentials (EP), tolerance maxima to painful tooth pulp stimuli, and subjective intensity ratings were measured as indicators of drug induced perception differences. After nalbuphine, the EP amplitudes markedly decreased while the stimuli of each modality were rated by the subjects to be of higher intensity. Also, the tolerance maxima of painful tooth pulp stimulation were reduced by nalbuphine, and naloxone did not have additional effects. In contrast, after aspirin and meperidine, the subjective pain ratings corresponded to the reduction of nociceptive EP amplitudes. Tolerance maxima to painful stimulation were also increased by both drugs. While aspirin did not influence acoustic and visual perception, meperidine caused a slight increase in EP amplitudes as well as in the intensity ratings of these stimuli relative to placebo. Thus, at the dose studied, nalbuphine did not act analgetically. The amplitude reduction of nociceptive EP suggested that nalbuphine had analgetic properties. These were, however, not confirmed by subjective pain ratings nor by changes in tolerance maxima.