As part of a study investigating new methods of detecting adverse drug reactions, adult outpatients receiving new prescriptions for 1 of 4 antibiotics (doxycycline, penicillin VK, ampicillin, or tetracycline) were assigned to 1 of 2 methods of monitoring adverse drug reactions. Data were collected from a total of 457 staff-initiated interviews and from 1467 patients who were asked to telephone to report possible adverse effects. Doxycycline is considered by authoritative sources to be generally comparable in side effects to other tetracyclines and penicillins, with the exception that it increases photosensitivity. Results from both monitoring methods consistently indicated at least a 3-fold higher frequency of nausea or vomiting with doxycycline relative to the other antibiotics. Complaints of skin rash also were at least 4 times more frequent with doxycycline, depending on the particular sample.