We treated 13 elderly patients with chronic mycobacterial lung disease with clarithromycin using 1000 mg b.i.d. as monotherapy. Patients had a mean age of 70 years, and 12 of 13 had creatinine clearances of 31-71 ml/min. Adverse events were seen in 100% of patients, with the most common being bitter taste (92%), nausea (92%), vomiting (54%) and central nervous system symptoms (54%). Elevated liver enzymes developed in five (38%) of 13 patients at weeks 1-6 of therapy. Mean serum levels of clarithromycin plus its 14-OH metabolite were 12.9 +/- 3.6 micrograms/ml (SD). There were 11 patients (85%) who discontinued the high dose within 3 months because of side effects. Serum drug levels of clarithromycin plus its 14-OH metabolite consistently exceeded 12 micrograms/ml in six of six patients who discontinued drug (10 of 10 values) compared with neither of two patients who tolerated the high dose (0 of 6 values). A dose reduction to 500 mg b.i.d. was well tolerated (nine of 10 patients). Future trials with clarithromycin in this population should use lower doses with attention to body mass and renal function to minimize side effects.