We report two patients with infectious mononucleosis-like syndrome induced by salazosulfapyridine (SASP). In both cases, high fever, skin rash, liver dysfunction and atypical lymphocytosis developed 3 weeks after initiating treatment with SASP. SASP is known to be mainly metabolized by N-acetyltransferase 2 (NAT2), and acetylation phenotypes (rapid, intermediate and slow acetylator) correlate with NAT2* genotypes. In our two patients, we investigated NAT2* genotypes by the polymerase chain reaction-restriction fragment length polymorphism method. We identified NAT2*6/*7 in one patient, and NAT2*6/*5 in the other, suggesting that both were slow acetylator phenotypes. In 20 healthy volunteers we found no slow acetylator genotypes. Genotyping prior to medication may be useful in evaluating patients with a high risk of severe systemic reaction to SASP.