Potassium deficiency in the rat results in growth retardation, muscle wasting and renal hypertrophy. This study tests the thesis that K deficiency leads to tissue distinct changes in the local IGF-I system and cell sensitivity to IGF-I that favors renal enlargement on the one hand and impaired muscle growth on the other. In rats after eight days of K deficiency, compared to pair-fed control rats, food utilization and muscle and body wt gain were attenuated while the kidneys enlarged. In muscle GH receptor and IGF-I gene expression, IGF-I peptide and IGF binding protein-5 (IGFBP) levels were decreased. Together with reduced food utilization, these changes may contribute to the attenuated muscle growth. In the enlarged kidneys despite a fall in IGF-I mRNA level, IGF-I peptide concentration was increased more than twofold. This increase in IGF-I could be caused by the increase in kidney IGFBP-1 gene and protein expression and the decrease in kidney IGF-I degrading activity noted in K deficiency. Treatment with IGF-I failed to induce body or muscle growth, but induced a further increase in kidney size and enlargement of the spleen. Thus, in K deficiency the spontaneous increase in IGF-I levels in the kidney that is IGF-I sensitive may well be a cause of the renal hypertrophy.