Although it is known that IGF-1 increases T lymphocyte proliferation, the regulation of its receptor expression during the process has not been defined. Consequently the regulation of IGF-1R expression by IGF-1 and the activation events in human blood T lymphocytes and the Jurkat T cell line were now investigated. IGF-1R expression in nonstimulated Jurkat cells was confirmed and downregulation by IGF-1 was demonstrated. In addition, both cell types showed a time-dependent reduction in the number of IGF-1R-positive cells following activation, which was increased by IGF-1. In Jurkat cells the negative regulation of IGF-1R levels was correlated with the appearance and continuous increase in IL-2R. In T lymphocytes the decrease in IGF-1R expression was faster, reaching its plateau after 3 h of activation. Our findings suggest that loss of the IGF-1R is one of the initial events of the activation process not regulated by IL-2.