Purpose. Imatinib treatment causes muscle cramps in up to 40% of patients, but their pathogenesis is unknown. We present a case series illustrating an association between imatinib, relative hypocalcaemia, and the development of cramps. Patients. The index patient developed muscle spasms and cramps after receiving imatinib for gastrointestinal stromal tumour (GIST) for 5 months. The adjusted serum calcium had dropped to the lower limit of normal. The low serum calcium and muscle cramps improved on stopping imatinib and recurred on rechallenge. We reviewed the medical records of 16 further patients. Results. Two patients reported muscle cramps (12%). There was a rapid and sustained reduction in adjusted serum calcium in the first 6 months from 2.45 +/- 0.11 mmol/L (mean +/- SD) to 2.30 +/- 0.08 mmol/L (p = 0.025). Conclusion. Imatinib treatment of GIST is associated with reduction in serum calcium which may explain the development of neuromuscular symptoms. In patients receiving imatinib, serum electrolytes should be monitored and muscle cramps treated by correction of serum calcium, or an empirical trial of quinine sulphate.