Patients with congenital or acquired disorders of antibody production suffer from a wide variety of infections. They are most often bacterial and due to Haemophilus influenzae or Streptococcus pneumoniae. Chronic pulmonary disease accounts for most of the deaths. While non-urogenital tract infections due to Ureaplasma urealyticum or other mycoplasmas are unusual in individuals with normal resistance, patients with antibody deficiency demonstrate a unique susceptibility. With increasing frequency, patients with impaired humoral immunity have been shown to have a mycoplasmal infection that results in pneumonitis, sinusitis, cystitis, arthritis, osteomyelitis, or cellulitis. The mycoplasmas may be responsible for chronic sinopulmonary disease in a majority of such patients. Awareness of the role these organisms play in causing infection in antibody-deficient patients and the institution of appropriate antibiotic therapy will contribute to an improvement in clinical outcome.