Effective biochemical control of GH and IGF-I levels in subjects with acromegaly can reduce mortality to that of the general population. Several retrospective studies have reported that the increased mortality is improved if GH levels are reduced to <2.5 microg/l, measured as mean of GH day profile or random GH level. It has been proposed that control or "cure" of disease is achieved when mean GH levels are <2.5 microg/l, nadir GH after an oral glucose load is <1 microg/l, and circulating IGF-I is reduced to an age- and sex-adjusted normal range. However, virtually all evidence from epidemiological studies has related GH values and not IGF-I values to long-term morbidity and mortality; controversy remains regarding the relative importance of these 2 parameters in determining post-treatment control status. Review of the West Midlands Acromegaly Database (419 patients) revealed that mortality was increased in the subgroup of patients with GH levels >2 microg/l (measured either as mean GH day profile or GH values across an oral glucose tolerance test, or random GH level). Factors influencing mortality in acromegaly were analyzed in a study from New Zealand of 208 acromegalic subjects. Serum GH at last follow-up was the most significant predictor of mortality, with mortality rates reduced to normal by achieving GH concentrations <1-2 microg/l. A nationwide survey of mortality in 334 patients with acromegaly from Finland has reported no difference in overall mortality between patients and general population; however, patients with last known basal serum GH >2.5 microg/l showed excess mortality (SMR 1.61, p<0.001). These 3 analyses of 961 patients indicate unequivocally that a GH value of 1-2 microg/l is an appropriate therapeutic target, as values above this level are associated with increased mortality.