Survivors of childhood cancer have been reported to have a severalfold increased risk of death from cardiovascular disease. A cluster of metabolic abnormalities, including obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, and dyslipidemia, have been designated as forming a metabolic syndrome that is associated with increased cardiovascular mortality. We studied 50 survivors (23 males) of childhood cancer, aged 10.5-31.2 yr, an average of 12.6 yr (range, 7.9-21.3 yr) after their diagnosis and compared them with 50 age- and sex-matched controls for signs of the metabolic syndrome by examining clinical and anthropometric measures, serum lipid profile, and fasting plasma insulin and glucose concentrations. Spontaneous nocturnal GH secretion was also evaluated in the cancer survivors. The patients had increased relative weight (P = 0.03) and body fat mass (P < 0.001), decreased serum high density lipoprotein (HDL) cholesterol (P < 0.001), and a reduced ratio of HDL to total cholesterol (P = 0.01). Fasting plasma glucose and insulin levels were higher (P < 0.001 and P = 0.003, respectively) in the cancer survivors than in the controls. The patients had an increased risk [odds ratio (OR), 4.5; 95% confidence interval (CI), 1.3-15.8; P = 0.01] of obesity (relative weight, > 120%), fasting hyperinsulinemia ( > 111 pmol/L; OR, 3.0; 95% CI, 1.0-8.6; P = 0.04), and reduced HDL cholesterol ( < 1.07 mmol/L; OR, 7.9; 95% CI, 2.2 to 29.6; P < 0.001). A combination of obesity, hyperinsulinemia, and low HDL cholesterol was seen in eight cancer survivors (16%), but in none of the controls (P = 0.01). This high risk group was characterized by reduced spontaneous GH secretion (P = 0.02). Long term survivors of childhood cancer appear to have an increased risk of manifestations of the metabolic syndrome. Decreased GH secretion may contribute to these metabolic abnormalities.