The cause of short stature in African Pygmies is unknown, but some evidence suggests that they are GH resistant. Since IGF-I mediates many actions of GH, we sought to determine if Pygmy tissue is responsive to IGF-I. We established HTLV-II-transformed cell lines from 1 Efe Pygmy, 1 African control, and 3 American controls, and quantified in vitro colony formation in response to IGF-I, GH, and insulin, and assessed IGF-I receptor binding. The Pygmy T-cell line showed no clonal responsiveness following stimulation with physiologic concentrations of IGF-I or any concentration of GH, but responded normally to insulin. IGF-I binding studies showed no binding to the Pygmy T-cell line with normal binding to control cells. The primary abnormality in this Pygmy T-cell line is IGF-I resistance at the receptor level with secondary GH resistance.