The pyridostigmine (PD)/growth hormone-releasing hormone (GHRH) stimulation test was used to determine growth hormone (GH) secretion in patients with pituitary adenomas prior to (n = 55) and after (n = 72) transsphenoidal adenomectomy, as well as in 98 controls. In controls, maximum concentrations of GH showed a strong negative relationship both with body mass index (BMI) and age. Having calculated the 95% confidence intervals for maximum GH concentrations to be expected for any given age and BMI according to a statistical model, we compared these individually predicted ranges to GH concentrations actually observed in patients with pituitary disease during PD/GHRH stimulation. Preoperatively and postoperatively, a maximum GH concentration below the calculated confidence intervals was seen in 29 of 55 (52%) and in 57 of 72 (79%) of these patients, respectively. In the remaining patients, maximum GH concentrations were in or above the range defined by these confidence intervals. Our results indicate that maximum concentrations of GH during the PD/GHRH test depend to a large extent on the individuals' age and BMI. The results obtained with the PD/GHRH stimulation must, in each individual patient, be compared with a large control group taking into account both age and BMI. In individuals older then 55 years and with a BMI greater than 35 kg/(2), the diagnosis of GH deficiency cannot safely be made, at least not with this test.