We report on three patients who developed fever after starting treatment with the anti-neoplastic agent, hydroxyurea. Fever occurred within 5 days to 3 weeks after starting treatment. In all cases the causal relationship between fever and use of hydroxyurea was demonstrated by spontaneous recovery after drug withdrawal and was confirmed by recurrence of fever after rechallenge. Other causes were excluded. Fever was accompanied by rash, gastro-intestinal and pulmonary symptoms, and arthralgia. Physicians should be aware of the fact that unexplained fever may be caused by hydroxyurea.