During an outbreak of pertussis in residents and staff of a facility for the developmentally disabled, 149 persons had laboratory evidence of Bordetella pertussis infection; 130 (87%) reported respiratory illness. Infection rates (IR) in affected wards ranged from 6% to 91%. Most residents were adolescents and adults and had received a full course of diphtheria-tetanus toxoids-pertussis (DTP) vaccine; IRs increased with increasing time after the last DTP dose in fully vaccinated residents. The IR was lower in residents on wards where erythromycin treatment/prophylaxis was started two or fewer weeks after the onset of illness in the first case on the ward (IR, 16%), compared with four or more weeks after onset (IR, 75%; P less than 10(-6)). Respiratory symptoms were milder in ill residents treated within seven days of onset of illness. Although B. pertussis transmission was substantial, erythromycin treatment of patients and prophylaxis of exposed persons was effective in decreasing transmission and disease severity. Carbamazepine toxicity occurred in seven (19%) of 37 residents when carbamazepine was administered with erythromycin.