A set of twins born to a 24-year-old primigravida had evidence of sepsis 24 to 60 hours after birth and were treated empirically with penicillin and gentamicin. A non-encapsulated H. influenzae biotype IV strain was isolated from the blood cultures of both and from the CSF of twin II. The isolates were beta-lactamase positive and hence showed resistance to ampicillin and therapy was changed to chloramphenicol only. Twin II recovered but Twin I developed a brain abscess in the left occipital region which resolved with extended antibiotic treatment. Although ampicillin-resistant H. influenzae have been reported in Malaysia, invasive disease by such strains are rare.