The gastric hormone ghrelin increases appetite and energy intake when administered by intravenous infusion to human subjects and has recently been reported to increase energy intake in patients with anorexia of cancer. Ghrelin also stimulates growth hormone release. We have now investigated whether subcutaneous administration of ghrelin is effective. Approval of the local ethics committee was obtained. Following a preliminary dose-finding study, 16 lean healthy volunteers received subcutaneous injections of ghrelin (3.6nmol/kg) or saline on two separate days after an overnight fast. Thirty minutes later a buffet breakfast was served. Food intake, appetite scores (visual analogue scales) and growth hormone were measured. On the saline day the mean increment in growth hormone was -0.8 plus/minus 2.3 mIU/l while on the ghrelin day the mean increment was 110.6 plus/minus 20.7 mIU/l. Subcutaneous ghrelin injection was associated with significant increase in meal energy intake (ghrelin injection 1308.1 plus/minus 164.2 kcal versus saline injection1079.5 plus/minus 148.7 kcal, p=0.04). This represents an increase of 29.8 plus/minus 10.1 % compared to saline. Ghrelin injection was without significant discomfort and appeared to enhance palatability of the food offered. Mean score for the question 'how pleasant did the food taste?' was 67.4 plus/minus 5.5 on the saline day and 82.7 plus/minus 4.6 on the ghrelin day (p=0.02). Thus ghrelin administered by subcutaneous injection was fully active and stimulated energy intake and meal appreciation and may provide a practical approach in the treatment of appetite loss.