One hundred forty-two children with purulent nasopharyngitis were randomized to four treatment groups with an antibiotic (cephalexin) alone or combined with a decongestant/antihistamine (pseudoephedrine/triprolidine) or their corresponding placebo equivalents. Follow-up evaluations by parents and physicians and bacteriologic evaluations were performed after 5 to 6 days of therapy. Groups were comparable with regard to age, sex, race, number of patients withdrawn from the study, fever greater than 38.0 degrees C, appearance of nasal discharge, nasal crusting and number of days until follow-up. Initial cultures from patients grew: Streptococcus pneumoniae, 46%; Haemophilus influenzae type b, 21%; and Streptococcus pyogenes, 8%. Nasal crusting was significantly associated with the growth of S. pneumoniae or H. influenzae type b. There were no significant differences between active drug and placebo treatment groups for change in nasal discharge, complications or apparent drug benefit. Cephalexin therapy did not result in a decrease in cultivation of pathogenic organisms from the nasopharynx. Significantly more side effects were attributed to pseudoephedrine/triprolidine treatment than to placebo. Routine culture or treatment of purulent nasopharyngitis should not be considered unless future controlled clinical trials demonstrate some therapeutic benefit.