A 19-month-old girl with developmental delay was found to have moderately elevated plasma citrulline and mildly elevated plasma arginine concentrations. Dietary history revealed that she consumed large quantities of watermelon (Citrullus vulgaris), a fruit containing high free citrulline and arginine concentrations. In order to determine whether the patient's high watermelon intake could account for her elevated plasma citrulline and arginine concentrations, we studied the response of plasma citrulline and arginine to ingestion of watermelon in six healthy adult volunteers. All developed markedly elevated plasma citrulline (mean maximum 593 micromol/L, range 386-1069) and moderately elevated plasma arginine (mean maximum 199 micromol/L, range 128-251). Physicians and laboratory personnel performing metabolic investigations should be aware of watermelon-induced citrullinaemia. Its hallmarks are elevated plasma citrulline, and to a lesser extent arginine, in the absence of orotic or arginosuccinic aciduria or hyperammonaemia. This phenomenon has implications for the management of patients with urea cycle and related disorders.