Compliance with self-administered therapy in pediatric and adolescent patients is not always complete. Noncompliance may result in erroneous conclusions about the efficacy of a given therapy and lead to unnecessary tests and alteration of treatment regimens. To examine the causes of noncompliance, 46 cancer patients aged 2.5 to 23 years (mean age, 6.85 years) and 40 parents were extensively interviewed at 2 weeks, 20 weeks, and 50 weeks post-diagnosis. The results of self-reported compliance were corroborated by serum bioassay of the prescribed medications. A significant correlation between the age of patient and compliance with chemotherapeutic agents and nonchemotherapeutic medications was found (P less than 0.05 and P less than 0.02, respectively), with adolescent patients being compliant less often. Over the course of therapy, compliance among patients decreased, but not significantly. A significant negative correlation was found between compliance and the number of children in the family. Compliers and noncompliers did differ significantly in how well they understood instructions concerning how to take their medication (P = 0.04). No significant correlations between compliance and stage of the disease, number or type of drugs used, complexity of the regimen, degree of satisfaction with information given to the patient, understanding of disease, treatment, or belief in medication efficacy were found. The main reasons given for noncompliance were forgetfulness, busy schedules, and nonavailability of medication. More compliers than noncompliers were in agreement with their parents regarding who was responsible for the administration of the medication. Compliance is a complex and multifaceted issue which interrelates with a large number of medical and social factors.