Peripheral blood leukocyte counts were performed in 167 children with acute otitis media who underwent myringotomy with culture of the middle ear exudate. A markedly elevated (greater than 97th percentile for age) leukocyte count was noted at initial presentation among 28% of these children, and counts exceeded 20,000/microL among 9%. Children older than six years were more likely than younger children to have marked leukocyte (41 v 24%, P less than 0.1). Children with culture-positive and culture-negative acute otitis media had similar leukocyte counts. There was no difference in frequency of posttreatment leukocytosis between those children who had complete resolution of acute otitis media and those children who had persistent otitis media with effusion. At follow-up 10 to 14 days later, relative leukopenia was observed significantly more often than at initial presentation (13 v 2%, P less than 0.001), and was most common among children two to five years old. Absolute neutropenia was likewise more common at the follow-up than at initial presentation (10 v 2%, P less than 0.01). Children treated with the fixed combination of erythromycin ethyl succinate-sulfisoxazole acetyl were somewhat more likely to have absolute neutropenia than those children who were treated with amoxicillin, but this difference was not statistically significant (14 v 6%, P less than 0.1). Acute otitis media, and perhaps the specific antibiotic therapy prescribed for acute otitis media, may exert marked effects upon peripheral blood counts.(ABSTRACT TRUNCATED AT 250 WORDS)