During high-dose methotrexate therapy we recognized a significant increase in AVP secretion as it has previously been reported for other cytostatics. We observed an excessive augmentation of AVP excretion in 24 h urine in 9 patients receiving high-dose methotrexate combined with a considerable water retention. The pathomechanism is so far unknown. From experimental data it may be assumed that methotrexate alters directly the neurosecretory areas of the cerebrum as well as effects the distribution of body fluid volumes. The considerable risk of a water intoxication seems to be of highly clinical importance.