A double-blind, randomized, crossover study assessed the effects of theophylline on behavior, mood, and efficiency of cognitive processing. Thirty-one children aged 8 to 12 years with moderate asthma were randomly assigned to 10-day theophylline followed by placebo or to placebo followed by theophylline experimental conditions separated by 2-day washout periods. Theophylline plasma concentrations and pulmonary function tests were performed throughout the study. Cognitive functioning tests and self-report measures were administered at baseline and after each medication phase. Behavior ratings were obtained from parents and teachers. Parents' and teachers' ratings did not reflect a theophylline effect on attention or activity level; children's self-reports showed no changes in mood, and no statistically significant differences were found on measures of cognitive processing. Large individual differences in sensitivity to theophylline effects were present. Although most of the children tolerated theophylline well, those already having attentional or achievement problems appeared vulnerable to adverse effects. Individual response differences should be a focus of future studies.