BACKGROUND Clarithromycin was used to treat lower respiratory tract infection in several developmentally disabled men who were also taking carbamazepine for seizure disorder. METHODS We studied retrospectively the use of clarithromycin in 5 patients taking carbamazepine. Because a drug interaction was suspected, the carbamazepine dosage was decreased during treatment, and serum levels were measured 3 to 5 days after change in therapy. In this study, we compared these findings with the base-line pretreatment and posttreatment dosage and serum levels of carbamazepine. RESULTS Despite decreasing the dosage of carbamazepine by 30 to 40 percent, the serum levels of this drug increased in all of our patients while taking clarithromycin, including 3 patients who developed toxic serum levels of carbamazepine. CONCLUSIONS There is a serious drug interaction between carbamazepine and clarithromycin. If possible, we believe that using clarithromycin should be avoided in patients taking carbamazepine. If clinical judgment suggests clarithromycin should be used, however, we suggest decreasing the dosage of carbamazepine by 30 to 50 percent, monitoring the serum drug levels closely, and warning the patient about the signs and symptoms of carbamazepine toxicity.