Objective: The concentrations of thyroid function determinants may change during severe illness. Our goal was to quantify their changes in children with cancer during chemotherapy, and to correlate them to clinical condition and type of drugs. Design: During a 3-month period all patients admitted for chemotherapy to the paediatric oncology ward were evaluated for inclusion. Patients with brain tumours, neuroblastoma (cranio)spinal irradiation and use of dexamethasone before the first blood sample were excluded. Measurements: Plasma concentrations of T4, T3, rT3, thyroxine-binding globulin (TBG), thyroglobulin (Tg), TSH, IGF-1, cortisol, PRL and physical well-being by means of questionnaires were measured before and during chemotherapy. Results: In 19 children, 46 courses of chemotherapy and 123 plasma samples were analysed. During chemotherapy, mean concentrations of TSH, T3, Tg and cortisol decreased to 53, 67, 69 and 15% of the baseline value, respectively. Mean plasma rT3 increased to 217% of baseline. In 87% of all courses, one or more thyroid parameter(s) was aberrant. Furthermore, in 23 samples (19%) from 10 patients (53%), the concentration of IGF-1 was below the reference value (adjusted for sex and age). Small changes were seen in scores for clinical condition but none was related to a change in thyroid function determinant. Most changes in thyroid hormones could be attributed to using dexamethasone. Conclusions: These results demonstrate that, in children, thyroid hormone state changes significantly during chemotherapy, apparently not related to physical well-being but to the drugs administered. Future investigations should focus on the impact for patient care and possibilities of (preventive) intervention.