Erythromycin was the first macrolide used clinically, and it is still the most widely prescribed in spite of reports of gastrointestinal side-effects. Erythromycin was given iv or orally to fasted and fed dogs with sensors implanted on the gastrointestinal tract for the measurement of motility. There was a large increase in stomach and upper small bowel contractile activity, accompanied by nausea and vomiting, while the distal small bowel appeared inhibited. Similar effects were seen in man. By contrast, two 16-membered macrolides, spiramycin and josamycin, did not produce such side-effects when given either orally or intravenously to dogs.