OBJECTIVE Growth hormone (GH) release is influenced by several factors including age, gender, physical exercise, nutritional status, sex steroids and body composition. The relationship with body composition is complex. Obesity is accompanied by suppression of spontaneous and stimulated GH release. As increasing body fat reduces stimulated GH secretion following a standard provocative test, the potential clinical uses of GH-releasing peptides (GHRPs), therapeutically or diagnostically, may be dependent on the relationship between body fat and GHRP-stimulated GH release. We have therefore assessed the effect of body composition and gender on the GH releasing capacity of hexarelin. METHODS A single bolus of subcutaneous hexarelin at a dose of 1.5 micrograms per kg of body weight was administered at time 0. Blood samples were taken at -10, 0, 10, 20, 30, 40, 50, 60, 90, 120, 170 and 180 min. METHODS Twenty-one (eight male) healthy elderly subjects with a median (range) age of 68 (60-81) years and BMI of 26 (19-30) kg/m2 were studied. METHODS Dual-energy X-ray absorptiometry (DEXA) was used to assess body composition. RESULTS Peak GH response correlated negatively with fat mass, BMI, percentage body fat, and weight [r = -0.72, P = 0.0001; r = -0.56, P = 0.009; r = -0.63, P = 0.002 and r = -0.48, P = 0.029, respectively,]. AUC GH correlated negatively with fat mass, BMI and percentage fat mass [r = -0.58, P = 0.006; r = -0.51, P = 0.019 and r = -0.66, P = 0.001 respectively]. Using multiple linear regression, fat mass was the most useful predictor for both peak GH response [R2 = 0.61, P < 0.0001] and AUC GH [R2 = 0.38, P = 0.003]. Gender was not a significant variable. CONCLUSIONS Increasing total fat mass results in a blunted GH response following subcutaneous hexarelin. Total fat mass appears to be a useful predictor of peak GH response even in normal individuals as none of the subjects in the present study was morbidly obese. This indicates that there is a continuum of effect of fat mass on hexarelin-stimulated GH release. Any impact of gender on the GH response to hexarelin is almost certainly indirect and mediated via differences in body composition. This observation will have an impact on the potential diagnostic and therapeutic uses of hexarelin and related GH secretagogues.