Acetazolamide, 500 mg 6 hourly, has been used to alkalinise the urine in patients receiving high dose methotrexate. A urinary pH of greater than 7.5 was achieved in every cycle (13 cycles in 10 patients). In 6 cycles a single supplementary dose of sodium bicarbonate was necessary. Plasma methotrexate levels fell satisfactorily at 24 and 48 h. Acetazolamide is a simple and effective method of achieving urinary alkalinisation with advantages over oral and intravenous bicarbonate.