This study compared the effects of moclobemide (Ro11-1163), a selective and reversible inhibitor of monoamine-oxidase (MAOI) type A and phenelzine, an irreversible non-selective MAOI, on the pressor responses to IV tyramine and norepinephrine. Because of the reversibility of this inhibition, the pressor effect of tyramine was expected to be minimal. Twelve healthy men participated in this randomized double-blind, placebo-controlled, crossover study. Volunteers began with oral treatment of moclobemide (100 mg TID) or phenelzine (15 mg TID) for 1 week followed by placebo treatment for 2 weeks and then moclobemide or phenelzine treatment for another week. The tyramine and norepinephrine challenge tests were conducted at baseline and then at weekly intervals, for a total of five challenges. The average tyramine dose that was required to increase systolic blood pressure by 25 mm Hg (PD25) was 1.6 +/- 0.2 mg after moclobemide treatment, which was lower (P less than .01) than the baseline value of 3.6 +/- 0.7 mg and that after phenelzine (3.0 +/- 0.5 mg) treatment. Moclobemide did not influence norepinephrine sensitivity. In conclusion, moclobemide mildly decreased the sensitivity to IV tyramine as compared with placebo and phenelzine.