The bindin of epidermal growth factor (EGF) and insulinlike growth factor I (IGF-I) to cell membranes was determined in 14 renal cancers and in 13 normal kidney tissues adjacent to the tumors. The soluble 34K IGF binding protein (34K IGF-BP) content and the phosphotyrosyl-protein phosphatase activity in renal cancer tissue and adjacent normal tissue were also determined. The specific EGF receptor binding in renal cancers was 12.7 f 2.5% (mean f SEM) as compared to 2.6 f 0.2% (mean f SEM) in normal tissues ( p < 0.01). Phosphotyrosyl-protein phosphatase activity in renal cancer tissue was less than half of that observed in normal renal tissue (p < 0.01). The highest IGF-I binding was observed in 5 renal cancers although no consistent differences between IGF-I binding to tumor and normal tissues were observed. Both EGF and IGF binding to kidney tissue were higher than binding to gastro-intestinal tissue irrespective of whether normal or malignant tissues were compared. All normal kidney tissues and 7 of 8 kidney tumors contained measurable amounts of 34K IGF-BP as determined by RIA and the cross-linking technique. In 2 tumor tissue samples the 34K IGF-BP content was increased 8and 15-fold over that seen in adjacent normal kidney tissue, whereas in the 6 other renal cancers the 34K IGF-BP was similar to that observed in normal kidney tissue.