The objective of this study is to investigate the performance of two novel tests in diagnosing growth hormone deficiency in adults. Fifty patients presenting with long-standing hypopituitarism and two control groups consisting of 50 healthy subjects in each group [age-, sex- and body mass index (BMI)-matched] participated in a multicentre study. All underwent two provocative tests on different days within 3 months apart: (i) a combined GHRH + GHRP-6 test and (ii) arginine + GHRH test. Main outcome measures were sensitivity, specificity and areas under receiver operating characteristic curves (ROC) for GHRH + GHRP-6 and arginine + GHRH tests in the diagnosis of GH deficiency in adults. A peak GH level after GHRH + GHRP-6, under 15.0 microg/l had a sensitivity of 94.4% and specificity of 98.8% for diagnosing GHD and area under the ROC curve was 0.99 (95% confidence interval 0.95-0.99). For peak GH levels after arginine + GHRH, a level under 9.6 microg/l had a sensitivity of 88.4% and specificity of 95% and area under the ROC curve of 0.96 (95% confidence interval 0.91-0.98). The relationship between the increment in serum GH following GHRH + GHRP-6 and arginine + GHRH test was positive, i.e. r = 0.749, P = 0.001.Thus, there was high concordance between both tests. Both GHRH + GHRP-6 and/or arginine + GHRH test may serve as an alternative to the ITT in diagnosing GHD in adults.