The in vitro activities of cefaclor, cefetamet, cefixime, cefotaxime and cefuroxime were determined against 150 isolates of Haemophilus influenzae. These included 50 ampicillin-susceptible, 50 beta-lactamase-producing and 50 intrinsically ampicillin-resistant isolates. A closer relationship was apparent between the intrinsic resistance to ampicillin and reduced susceptibility to cephalosporins. Both MIC and disc diffusion methods showed that the activities of cephalosporins were reduced against most, though not all, isolates with intrinsic resistance to ampicillin. All intrinsically ampicillin-resistant isolates should be considered resistant to all cephalosporins at the present time since the clinical significance of the reduction in susceptibility is uncertain. Amongst the five cephalosporins tested, cefaclor susceptibility may facilitate the detection of intrinsic ampicillin resistance since it predicts isolates with this type of resistance mechanism.