To determine whether systemic administration of antibiotics may eliminate or reduce the need for tympanomastoid surgery in chronic suppurative otitis media without cholesteatoma, we undertook a randomized, prospective study comparing three regimens: (1) daily suction and débridement, with intravenous administration of mezlocillin until 3 days after the discharge stopped, (2) daily suction and débridement, with intravenous use of ceftazidime until 3 days after the discharge stopped, and (3) daily suction and débridement without antibiotics. No topical antimicrobial agents were used during the study. Fifty-one patients were included, and 48 children completed the study. The duration of discharge from the ear before treatment was 2 to 123 months (median 20 months). In 26 patients (51%), the disease was bilateral. Aerobic cultures, obtained with the Alden-Senturia middle ear aspirator, yielded Pseudomonas aeruginosa in 98%, enteric gram-negative bacilli in 33%, staphylococci in 25%, and Haemophilus influenzae in 12%. The first 33 patients were randomly assigned to one of the three regimens. In the 21 patients treated with suction and antibiotics (either mezlocillin or ceftazidime), the discharge stopped completely, versus in only 1 (8%) of 12 patients in the suction-only regimen (p less than 0.01). Therefore the following 18 patients were randomly assigned to one of only two groups, which included the two suction-and-antibiotic regimens. In all patients treated initially with antibiotics, discharge stopped after 4 to 18 days (mean 12.0 days), but 25% needed treatment for greater than 14 days. Amoxicillin prophylaxis was administered to 27 (56%) of the patients after completion of therapy. All patients were followed for 6 months. Drainage recurred in 12 (25%) patients during the first 3 months after the study. The recurrence rate was not affected by the antibiotic regimen, the patient's age, the duration of drainage before initiation of antibiotic therapy, or prophylaxis. We conclude that intravenous wide-spectrum antibiotic therapy in conjunction with daily suction and débridement is efficacious for the treatment of chronic suppurative otitis media without cholesteatoma.