Erythromycin, the prototypical macrolide, has been widely used since the 1950s in the management of pediatric infections. Erythromycin is the drug of choice for infants and children with Legionnaire's disease, pertussis, diphtheria, lower respiratory tract infections caused by Mycoplasma pneumoniae, Chlamydia pneumoniae and Chlamydia trachomatis and enteritis caused by Campylobacter jejuni. It is also indicated for treatment of syphilis; for streptococcal, staphylococcal and pneumococcal infections; genital infections caused by Ureaplasma urealyticum; and for the prevention of rheumatic fever and endocarditis in patients who are allergic to beta-lactam antibiotics. The new macrolides azithromycin and clarithromycin are also active against Borrelia burgdorferi, Helicobacter pylori, Mycobacterium avium-intracellulare complex, Cryptosporidium spp. and Toxoplasma gondii. Erythromycin is associated with a low risk of serious side effects, although gastric distress occurs in a significant proportion of patients. Drug interactions with theophylline, carbamazepine, warfarin, cyclosporine, terfenadine and digoxin limit erythromycin use. The newer macrolides azithromycin and clarithromycin are more stable, better absorbed and better tolerated than erythromycin. Azithromycin is more active than erythromycin against Haemophilus influenzae. Excellent tissue and intracellular penetration may contribute to their clinical efficacy. In children both azithromycin and clarithromycin are indicated for acute otitis media caused by Streptococcus pneumoniae, H. influenzae and Moraxella catarrhalis and for pharyngitis/tonsillitis caused by Streptococcus pyogenes. (As of December, 1996, azithromycin for oral suspension was approved for community-acquired pneumonia in children caused by C. pneumoniae, H. influenzae, M. pneumoniae and S. pneumoniae.) Claritromycin is also indicated for acute maxillary sinusitis, uncomplicated skin and skin structure infections, pneumonia and disseminated mycobacterial infections. Azithromycin and clarithromycin are associated with a lower incidence of gastrointestinal side effects, a low rate of drug discontinuation caused by side effects and a low potential for interaction with other drugs.