In this issue, Nass and colleagues (17) report the effects of MK-677 on age-associated decreases in lean body mass and increases in body fat. The investigators conducted a 2-year, double-masked, placebo-controlled, modified-crossover, General Clinical Research Centerbased clinical trial in which 65 healthy men and women (of whom some were receiving hormone replacement therapy) 60 to 81 years of age received 25 mg of MK-677 each morning. The primary outcome measures at 1 year included 24-hour growth hormone secretory profiles, morning IGF-I serum concentrations, fat-free mass (determined by a 4-compartment model), and abdominal visceral fat. The study was powered on the 12-month change comparison between the MK-677 and placebo groups and did not evaluate possible effects of sex or hormone replacement therapy. Secondary outcome measures included various other body composition, endocrinemetabolic, strength, physical performance, and quality-of-life measures. After 1 year, circadian pulsatile growth hormone secretion and morning IGF-I concentration were augmented to those of healthy young adults. Fat-free (total body and limb lean) mass and intracellular water increased significantly, the latter being a biomarker of fat-free mass. Total and abdominal fat, muscle strength and function, and quality of life did not change. Low-density lipoprotein cholesterol levels decreased slightly, whereas cortisol, fasting blood glucose, and hemoglobin A1c levels increased. The Quicki index of insulin sensitivity decreased slightly. MK-677 was generally well tolerated. Appetite and body weight increased somewhat, but peripheral edema, joint or muscle pains, newly detected malignant disease, and other adverse outcomes did not significantly increase in women or men. Analysis of the 2-year outcome data in a subset of 53 of the 65 participants revealed that the growth hormone IGF-I and fat-free mass changes persisted. In participants treated for 2 years with MK-677, fasting blood glucose values were no longer elevated. Concentrations of IGF-I returned to normal 1 month after crossover and by 6 months after study completion. Nass and colleagues concluded that long-term functional and, ultimately, pharmacoeconomic studies are indicated in older adults.