The mechanism by which estradiol, testosterone, 1,25(OH)2vitamin D3, and triiodothyronine promote tissue growth is unknown, although, in some tissues, a role for local IGF-I has been suggested. We previously showed that HTLV-II-transformed T-cell lines from healthy adults augmented basal colony formation in response to peptide (growth hormone, parathormone, and adrenocorticotrophin) and glycoprotein (thyroid-stimulating hormone) hormones through stimulation of local IGF-I. T-cell lines from African Efe Pygmies, however, were resistant to the direct growth-promoting action of IGF-I, as well as to the growth-promoting action of growth hormone, parathormone, adrenocorticotrophin, and thyroid-stimulating hormone. We, therefore, used these cell lines to determine the mechanism of T-cell growth in response to steroid and thyroid hormones. We quantified colony formation of American control T-cell lines in the presence and absence of αIR-3 antibody against the type 1 IGF receptor and Pygmy T-cell lines in response to estradiol (36.7–1835 pmol/ liter), testosterone (34.7–17,350 pmol/liter), 1,25(OH)2vitamin D3(2.4–24,000 pmol/liter), and triiodothyronine (1536–192,000 pmol/liter). There were no statistically significant differences by ANOVA in overall response curves for any of the four hormones comparing control clonal responses in the presence or absence of αIR-3 and no statistically significant difference in overall responsiveness between control and Pygmy T-cell lines. From these data, we conclude that (i) normal T-cell lines grow in response to estradiol, testosterone, 1,25(OH)2vitamin D3, and triiodothyronine; (ii) these responses are not mediated through local IGF-I since they are not blocked by pretreatment with antibody to the type 1 IGF receptor; and (iii) Pygmy T-cell lines, which are genetically resistant to IGF-I, grow equivalently to control T-cell lines in response to estradiol, testosterone, 1,25(OH)2vitamin D3, and triiodothyronine, further underscoring the IGF-I independence of this stimulation in our system.