This pilot study was designed to determine the serum cytokine profile of acute otitis media (AOM) due to Streptococcus pneumoniae and the impact of clarithromycin (Abbott Laboratories, Inc). Serum levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-8 were measured at diagnosis and 3 to 5 days after start of antibiotic treatment in 10 patients (mean age, 18.3 +/- 13.9 months) who had middle ear fluid culture positive for S. pneumoniae. The mean concentrations of all cytokines were elevated at diagnosis of AOM compared to levels in healthy controls, yet only IL-6 reached statistical significance (P = 0.05). IL-6 showed a statistically significant decrease in mean serum concentration at visit 2 (P = 0.03). IL-8 displayed a similar pattern to IL-6, but the difference between samples from day 1 and day 2 did not reach statistical significance. The cytokines IL-1 beta and TNF-alpha appear to be elevated in the serum of patients with S. pneumoniae AOM, but there was no significant change between mean serum levels obtained pre- and postinitiation of antibiotic treatment in the time frame studied. The results suggest a systemic inflammatory response as evidenced by increased IL-6. A significant decrease of IL-6 and improvement of clinical symptoms were observed. Determining cytokine levels, especially IL-6, in AOM could offer a powerful tool for objective assessment of response to treatment, minimizing unnecessary treatment of asymptomatic children who may still have some otoscopic findings suggestive of AOM at follow-up visits.