Earlier studies have suggested that patients with slow acetylation phenotype were more likely to respond to phenelzine treatment and more likely to experience side effects. The metabolism of phenelzine has not been extensively investigated in humans because of limitations in analytical methodology. A labeled form of phenelzine is required for metabolite identification because these same compounds can arise from endogenous substances e.g., phenylacetic acid. The use of a stable isotope-labeled compound has the advantage that in vivo studies can be performed without radiation exposure. Site-specific, stable isotope-labeled phenelzine analogs were synthesized and used in metabolic and pharmacokinetic studies in humans. The authors were unable to detect N-acetylphenelzine in any urine or plasma samples. The major metabolites phenylacetic acid and parahydroxyphenylacetic acid constitute up to 79% of the administered dose excreted via the urine in the first 96 hours. These studies indicate that N-acetylation of phenelzine is not a significant metabolic pathway in humans, which helps explain recent clinical studies that failed to find an association between acetylation phenotype and clinical effects of phenelzine.