Two acromegalic patients with severe headache, persisting after pituitary adenomectomy followed by radiotherapy in one, were treated with the somatostatin analogue SMS 201–995. Both had been resistant to conventional headache therapy and experienced dramatic and rapid relief after the first injection of the analogue. This result persisted with long-term treatment of the drug. Although the mechanism of action of SMS 201–995 in pain remains unclear, the rapid and efficacious analgesic effect of this compound may be one more indication for its use in pituitary tumors associated with cephalalgias.