Single-drug resistance to tetracycline, doxycycline, erythromycin, or fluoroquinolones in Campylobacter isolates recovered from humans has been documented worldwide. Multidrug resistance to these antibiotics is rare in Campylobacter jejuni. We report the sequential development of multidrug resistance in C. jejuni isolates from three patients who were infected with human immunodeficiency virus. Multiple isolates recovered from stool specimens from these patients were ribotyped, and antibiotic susceptibility profiles were determined. The results indicated that each patient was infected with a single strain of C. jejuni that had progressively acquired resistance to the antibiotics used during treatment. The emergence of resistant isolates appeared to correlate with clinical relapse. In these patients, campylobacter enteritis was prolonged, severe, and relapsing, and antimicrobial therapy was required. Once these first-line antibiotics become ineffective, few other antibiotics are available for treating patients with campylobacter enteritis. Acquisition of antibiotic resistance in C. jejuni is therefore of concern in these cases.