Surveys carried out using a chromogenic cephalosporin test for beta-lactamase production (ampicillin resistance) among isolates of Haemophilus influenzae in Johannesburg have indicated an appreciable prevalence, especially among children seen at the new Johannesburg Hospital. Of type b strains recovered from these children, 10,9% were ampicillin-resistant. Three of the last 10 cases of serious systemic H. influenzae infections encountered at the Johannesburg Hospital were caused by beta-lactamase-producing strains, all of these having been acquired in the community rather than in hospital. These findings suggest that the optimal initial starting treatment for serious systemic or life-threatening H. influenzae infections should include chloramphenicol, either alone or at least in conbination with ampicillin or a similar compound.