Children with normal-variant short stature can be classified into four subgroups by measuring their anabolic and growth reactions to a 10-day course of human growth hormone. In Subgroup 1 there is no anabolic or growth reaction; in Subgroup 2 there is a weak anabolic reaction but no growth; Subgroups 3 and 4 have both reactions but Subgroup 4 is more responsive than Subgroup 3. We monitored growth rate and plasma immunoreactive somatomedin C concentrations in four to six children from each subgroup (age range, eight to 11 years) before, during, and after six months of injections of growth hormone (0.08 unit per kilogram of body weight per day). In children in Subgroups 3 and 4, the average somatomedin C level, which was subnormal before treatment, was restored to normal. Simultaneously, the average growth rate accelerated fivefold. In children in Subgroups 1 and 2, whose average pretreatment somatomedin C was normal, growth hormone had little effect on somatomedin level of growth rate. The somatomedin response in Subgroups 3 and 4 was apparent by the 10th day of treatment. This response provides a rapid method for identifying affected children who will benefit from longterm administration of human growth hormone.